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Clinical Trial Results:
A Phase 1/2, Open-label, Multi-center Study to Assess the Safety and Tolerability of Durvalumab (Anti-PD-L1 Antibody) as Monotherapy and in Combination Therapy in Subjects With Lymphoma or Chronic Lymphocitic Leukemia

Summary
EudraCT number	2015-003516-21
Trial protocol	GB DE NL IT
Global end of trial date	21 Aug 2022

Results information
Results version number	v2(current)
This version publication date	25 Oct 2023
First version publication date	06 Sep 2023
Other versions	v1
Version creation reason

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

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Trial information

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Sponsor protocol code

MEDI4736-NHL-001

ISRCTN number

US NCT number

NCT02733042

WHO universal trial number (UTN)

Sponsor organisation name

Bristol-Myers Squibb

Sponsor organisation address

Chaussée de la Hulpe 185, Brussels, Belgium, 1170

Public contact

EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com

Scientific contact

Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.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

20 Aug 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

21 Aug 2022

Was the trial ended prematurely?

Main objective of the trial

To assess the safety and tolerability of durvalumab when given in combination with lenalidomide and rituximab; ibrutinib; or bendamustine and rituximab in participants with lymphoma or chronic lymphocytic leukemia.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

11 May 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

France: 22

Country: Number of subjects enrolled

Italy: 23

Country: Number of subjects enrolled

Japan: 12

Country: Number of subjects enrolled

United Kingdom: 18

Country: Number of subjects enrolled

United States: 25

Country: Number of subjects enrolled

Netherlands: 6

Worldwide total number of subjects

106

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

106 participants were treated.

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

Part 1 Arm A: DUR 1500 + LEN 20

Arm description

Participants received durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent non-Hodgkin's lymphoma (NHL) or for all cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL.

Arm type

Experimental

Investigational medicinal product name

Lenalidomide

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Part 1 Arm A: DUR 1500 +LEN 20 +RIT 375

Arm description

Durvalumab (DUR) 1500mg IV infusion on Day 1 of Cycles 1 to 13 and lenalidomide (LEN) 20mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for subjects with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab (RIT) 375 mg/m² IV infusion on Days 2, 8, 15, and 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab (RIT) 375 mg/m² IV infusion on Days 2, 8, 15, and 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5

Investigational medicinal product name

Lenalidomide

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13

Part 1 Arm A: DUR 1500 +LEN 10 +RIT 375

Arm description

Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 10 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab (RIT) 375 mg/m² IV infusion on Days 2, 8, 15, and 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5

Investigational medicinal product name

Lenalidomide

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Lenalidomide (LEN) 10 mg orally once daily on Days 1 to 21 of Cycles 1 through 13

Part 1 Arm B: DUR 1500 + IBR 420

Arm description

Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib (IBR) 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Investigational medicinal product name

Ibrutinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Ibrutinib (IBR) 420 mg orally once daily

Part 1 Arm B: DUR 1500 + IBR 560

Arm description

Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.

Arm type

Experimental

Investigational medicinal product name

Ibrutinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Ibrutinib (IBR) 560 mg orally once daily

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Part 1 Arm C: DUR 1500 + RIT 375

Arm description

Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).

Arm type

Experimental

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Part 1 Arm C: DUR 1500 + BEN 70

Arm description

Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and bendamustine (BEN) 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.

Arm type

Experimental

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravesical use

Dosage and administration details

Bendamustine (BEN) 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Part 1 Arm C: DUR 1500 +RIT 375 +BEN 70

Arm description

Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravesical use

Dosage and administration details

Bendamustine (BEN) 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).

Part 1 Arm C: DUR 1500 + RIT 375 + BEN 90

Arm description

Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 90 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravesical use

Dosage and administration details

Bendamustine (BEN) 90 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).

Part 2 Arm B CLL/SLL: DUR 1500 + IBR 420

Arm description

Participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.

Arm type

Experimental

Investigational medicinal product name

Ibrutinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Ibrutinib (IBR) 420 mg orally once daily

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Part 2 Arm B MCL: DUR 1500 + IBR 560

Arm description

Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.

Arm type

Experimental

Investigational medicinal product name

Ibrutinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Ibrutinib (IBR) 560 mg orally once daily

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Part 2 Arm C FL: DUR 1500 + RIT 375 + BEN 70

Arm description

Participants with follicular lymphoma (FL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravesical use

Dosage and administration details

Bendamustine (BEN) 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6

Part 2 Arm C DLBCL: DUR 1500 + RIT 375 + BEN 70

Arm description

Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravesical use

Dosage and administration details

Bendamustine (BEN) 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6

Part 2 Arm C CLL/SLL:DUR 1500 +RIT 375 +BEN 70

Arm description

Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravesical use

Dosage and administration details

Bendamustine (BEN) 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.

Part 2 Arm D FL: DUR 1500

Arm description

Participants with follicular lymphoma received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Part 2 Arm D DLBCL: DUR 1500

Arm description

Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Part 2 Arm D CLL/SLL: DUR 1500

Arm description

Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Part 2 Arm D MCL: DUR 1500

Arm description

Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Part 2 Arm D HL: DUR 1500

Arm description

Participants with Hodgkin lymphoma (HL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Arm type

Experimental

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13

Number of subjects in period 1	Part 1 Arm A: DUR 1500 + LEN 20	Part 1 Arm A: DUR 1500 +LEN 20 +RIT 375	Part 1 Arm A: DUR 1500 +LEN 10 +RIT 375	Part 1 Arm B: DUR 1500 + IBR 420	Part 1 Arm B: DUR 1500 + IBR 560	Part 1 Arm C: DUR 1500 + RIT 375	Part 1 Arm C: DUR 1500 + BEN 70	Part 1 Arm C: DUR 1500 +RIT 375 +BEN 70	Part 1 Arm C: DUR 1500 + RIT 375 + BEN 90	Part 2 Arm B CLL/SLL: DUR 1500 + IBR 420	Part 2 Arm B MCL: DUR 1500 + IBR 560	Part 2 Arm C FL: DUR 1500 + RIT 375 + BEN 70	Part 2 Arm C DLBCL: DUR 1500 + RIT 375 + BEN 70	Part 2 Arm C CLL/SLL:DUR 1500 +RIT 375 +BEN 70	Part 2 Arm D FL: DUR 1500	Part 2 Arm D DLBCL: DUR 1500	Part 2 Arm D CLL/SLL: DUR 1500	Part 2 Arm D MCL: DUR 1500	Part 2 Arm D HL: DUR 1500
Started	3	3	8	3	4	3	1	4	5	10	10	10	10	5	5	10	2	5	5
Entered follow-up	3	3	6	3	2	2	0	4	4	4 ^[1]	5	9	9	4	1	5	0	3	2
Completed	0	1	1	0	1	0	0	1	0	6	4	4	1	1	0	0	0	0	1
Not completed	3	2	7	3	3	3	1	3	5	4	6	6	9	4	5	10	2	5	4
Adverse event, serious fatal	-	-	-	-	-	-	1	-	1	-	1	-	-	-	1	2	-	-	-
Consent withdrawn by subject	-	1	2	1	1	-	-	-	1	1	-	2	1	1	-	-	-	-	-
Adverse event, non-fatal	1	-	1	1	-	-	-	-	-	-	2	2	-	2	-	-	-	1	-
Other Reasons	-	-	1	-	-	-	-	-	-	1	1	-	-	-	-	1	-	1	-
Progressive Disease	2	1	3	1	2	3	-	3	3	2	2	2	8	1	4	7	2	3	4

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: 106 participants were treated. 69 participants entered follow-up period after completing or discontinuing study treatment.

Baseline characteristics

Top of page

Reporting group title

Part 1 Arm A: DUR 1500 + LEN 20

Reporting group description

Reporting group title

Part 1 Arm A: DUR 1500 +LEN 20 +RIT 375

Reporting group description

Reporting group title

Part 1 Arm A: DUR 1500 +LEN 10 +RIT 375

Reporting group description

Reporting group title

Part 1 Arm B: DUR 1500 + IBR 420

Reporting group description

Reporting group title

Part 1 Arm B: DUR 1500 + IBR 560

Reporting group description

Reporting group title

Part 1 Arm C: DUR 1500 + RIT 375

Reporting group description

Reporting group title

Part 1 Arm C: DUR 1500 + BEN 70

Reporting group description

Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and bendamustine (BEN) 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.

Reporting group title

Part 1 Arm C: DUR 1500 +RIT 375 +BEN 70

Reporting group description

Reporting group title

Part 1 Arm C: DUR 1500 + RIT 375 + BEN 90

Reporting group description

Reporting group title

Part 2 Arm B CLL/SLL: DUR 1500 + IBR 420

Reporting group description

Reporting group title

Part 2 Arm B MCL: DUR 1500 + IBR 560

Reporting group description

Reporting group title

Part 2 Arm C FL: DUR 1500 + RIT 375 + BEN 70

Reporting group description

Reporting group title

Part 2 Arm C DLBCL: DUR 1500 + RIT 375 + BEN 70

Reporting group description

Reporting group title

Part 2 Arm C CLL/SLL:DUR 1500 +RIT 375 +BEN 70

Reporting group description

Reporting group title

Part 2 Arm D FL: DUR 1500

Reporting group description

Participants with follicular lymphoma received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Reporting group title

Part 2 Arm D DLBCL: DUR 1500

Reporting group description

Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Reporting group title

Part 2 Arm D CLL/SLL: DUR 1500

Reporting group description

Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Reporting group title

Part 2 Arm D MCL: DUR 1500

Reporting group description

Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Reporting group title

Part 2 Arm D HL: DUR 1500

Reporting group description

Participants with Hodgkin lymphoma (HL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Reporting group values	Part 1 Arm A: DUR 1500 + LEN 20	Part 1 Arm A: DUR 1500 +LEN 20 +RIT 375	Part 1 Arm A: DUR 1500 +LEN 10 +RIT 375	Part 1 Arm B: DUR 1500 + IBR 420	Part 1 Arm B: DUR 1500 + IBR 560	Part 1 Arm C: DUR 1500 + RIT 375	Part 1 Arm C: DUR 1500 + BEN 70	Part 1 Arm C: DUR 1500 +RIT 375 +BEN 70	Part 1 Arm C: DUR 1500 + RIT 375 + BEN 90	Part 2 Arm B CLL/SLL: DUR 1500 + IBR 420	Part 2 Arm B MCL: DUR 1500 + IBR 560	Part 2 Arm C FL: DUR 1500 + RIT 375 + BEN 70	Part 2 Arm C DLBCL: DUR 1500 + RIT 375 + BEN 70	Part 2 Arm C CLL/SLL:DUR 1500 +RIT 375 +BEN 70	Part 2 Arm D FL: DUR 1500	Part 2 Arm D DLBCL: DUR 1500	Part 2 Arm D CLL/SLL: DUR 1500	Part 2 Arm D MCL: DUR 1500	Part 2 Arm D HL: DUR 1500	Total
Number of subjects	3	3	8	3	4	3	1	4	5	10	10	10	10	5	5	10	2	5	5	106
Age Categorical
Units: participants
< 65 Years	1	1	2	2	1	0	0	1	3	4	2	5	7	2	3	5	1	0	4	44
≥ 65 Years	2	2	6	1	3	3	1	3	2	6	8	5	3	3	2	5	1	5	1	62
Age Continuous
Units: years
median (full range (min-max))	71.0 (50 to 78)	66.0 (52 to 75)	77.0 (53 to 80)	58.0 (54 to 74)	68.0 (57 to 81)	79.0 (76 to 80)	70.0 (70 to 70)	68.0 (52 to 78)	38.0 (21 to 77)	68.0 (55 to 73)	73.5 (54 to 84)	64.5 (45 to 75)	60.0 (46 to 71)	68.0 (53 to 79)	52.0 (39 to 71)	61.5 (22 to 76)	62.0 (55 to 69)	77.0 (69 to 80)	51.0 (34 to 65)	-
Sex: Female, Male
Units: participants
Female	1	0	2	0	2	2	0	1	3	3	1	3	4	2	2	4	1	2	2	35
Male	2	3	6	3	2	1	1	3	2	7	9	7	6	3	3	6	1	3	3	71
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	2
Not Hispanic or Latino	2	2	7	2	3	1	1	3	3	5	7	6	8	3	2	9	2	5	5	76
Unknown or Not Reported	1	1	1	1	0	2	0	1	2	5	3	4	2	1	3	1	0	0	0	28
Race/Ethnicity, Customized
Units: Subjects
White	2	2	3	2	4	0	1	0	4	5	6	4	4	4	2	9	2	4	5	63
Asian	0	0	3	0	0	0	0	3	1	0	1	1	3	0	0	0	0	1	0	13
Black or African American	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Other	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	2
Not Collected or Reported	1	1	1	1	0	3	0	1	0	5	3	4	2	1	3	1	0	0	0	27
Histology
Units: Subjects
Follicular lymphoma	1	3	1	1	0	1	0	1	0	0	0	10	0	0	5	0	0	0	0	23
Diffuse large B-cell lymphoma	2	0	4	0	0	2	1	3	5	0	0	0	10	0	0	10	0	0	0	37
Marginal zone lymphoma	0	0	2	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	5
Transformed follicular lymphoma	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Mantle cell lymphoma	0	0	0	1	1	0	0	0	0	0	10	0	0	0	0	0	0	5	0	17
CLL / SLL	0	0	0	1	0	0	0	0	0	10	0	0	0	5	0	0	2	0	0	18
Hodgkin lymphoma	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	5	5
Eastern Cooperative Oncology Group ECOG) Performance Status
ECOG performance status is used to describe a patient’s level of functioning in terms of their ability to care for themselves, daily activity, and physical ability (walking, working, etc.). The scale ranges from 0 to 5: • 0 = Fully active, no restrictions; • 1 = Restricted activity but ambulatory, able to carry out work of a light nature; • 2 = Ambulatory and capable of all self-care but unable to carry out work activities; • 3 = Limited self-care, confined to bed or chair more than 50% of waking hours; • 4 = Completely disabled, no selfcare, confined to bed or chair; • 5 = Dead
Units: Subjects
0 - Fully Active	0	2	2	0	1	1	0	3	2	8	6	6	7	0	2	3	1	4	5	53
1 - Restricted but ambulatory	3	1	4	3	3	2	0	0	2	2	3	3	1	4	2	4	1	1	0	39
2 - Ambulatory but unable to work	0	0	2	0	0	0	1	1	1	0	1	1	2	1	1	2	0	0	0	13
3 - Limited self-care	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1

Subject analysis set title

Part 1, Arm C: DUR 1500 mg + RIT 375 mg/mÂ² + BEN 90 mg/m²

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mG

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Part 2 Arm C DLBCL: DUR + RIT 375 mg/m² + BEN 70 mg/m²

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Arm A: Durvalumab + Lenalidomide ± Rituximab

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants assigned to Arm A received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and 10 mg or 20 mg lenalidomide orally once daily on Days 1 to 21 of Cycles 1 to 13 in indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in aggressive NHL, and rituximab 375 mg/m² IV weekly in Cycle 1 and on Day 1 of Cycles 2 to 5.

Subject analysis set title

Arm B: Durvalumab + Ibrutinib

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants assigned to Arm B received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and 420 or 560 mg ibrutinib orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.

Subject analysis set title

Arm C: Durvalumab + Bendamustine ± Rituximab

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants assigned to Arm C received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, 70 or 90 mg/m² bendamustine IV on Days 1 and 2 of Cycles 1 to 6, and rituximab 375 mg/m² IV on Day 2 of Cycles 1 to 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).

Subject analysis set title

Arm D: Durvalumab Monotherapy

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants assigned to Arm D received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13.

Subject analysis set title

Arm D: Durvalumab Monotherapy

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants assigned to Arm D received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13.

Subject analysis set title

Arm A: Durvalumab + Lenalidomide Â± Rituximab

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Arm A: Lenalidomide 10 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in Arm A received lenalidomide 10 mg orally once daily on Days 1 to 21 of Cycles 1 to 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and rituximab 375 mg/m² IV weekly in Cycle 1 and on Day 1 of Cycles 2 to 5.

Subject analysis set title

Arm A: Lenalidomide 20 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in Arm A received lenalidomide 20 mg orally once daily on Days 1 to 21 of Cycles 1 to 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and rituximab 375 mg/m² IV weekly in Cycle 1 and on Day 1 of Cycles 2 to 5.

Subject analysis set title

Arm B: Ibrutinib 420 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants assigned to Arm B received 420 mg ibrutinib orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason, and durvalumab 1500 mg IV on Day 1 of Cycles 1 to 13.

Subject analysis set title

Arm B: Ibrutinib 560 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants assigned to Arm B received 560 mg ibrutinib orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason, and durvalumab 1500 mg IV on Day 1 of Cycles 1 to 13.

Subject analysis sets values	Part 1, Arm C: DUR 1500 mg + RIT 375 mg/mÂ² + BEN 90 mg/m²	Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mG	Part 2 Arm C DLBCL: DUR + RIT 375 mg/m² + BEN 70 mg/m²	Arm A: Durvalumab + Lenalidomide ± Rituximab	Arm B: Durvalumab + Ibrutinib	Arm C: Durvalumab + Bendamustine ± Rituximab	Arm D: Durvalumab Monotherapy	Arm D: Durvalumab Monotherapy	Arm A: Durvalumab + Lenalidomide Â± Rituximab	Arm A: Lenalidomide 10 mg	Arm A: Lenalidomide 20 mg	Arm B: Ibrutinib 420 mg	Arm B: Ibrutinib 560 mg
Number of subjects	5	10	10	14	27	38	26	25	14	5	4	13	13
Age Categorical
Units: participants
< 65 Years	3	4
≥ 65 Years	2	6
Age Continuous
Units: years
median (full range (min-max))	38.0 (21 to 77)	68.0 (55 to 73)	30.0 (6.7 to 65.2)
Sex: Female, Male
Units: participants
Female	3	3
Male	2	7
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	0	0
Not Hispanic or Latino	3	5
Unknown or Not Reported	2	5
Race/Ethnicity, Customized
Units: Subjects
White	4	5
Asian	1	0
Black or African American	0	0
American Indian or Alaska Native	0	0
Native Hawaiian or Other Pacific Islander	0	0
Other	0	0
Not Collected or Reported	0	5
Histology
Units: Subjects
Follicular lymphoma	0	0
Diffuse large B-cell lymphoma	5	0
Marginal zone lymphoma	0	0
Transformed follicular lymphoma	0	0
Mantle cell lymphoma	0	0
CLL / SLL	0	10
Hodgkin lymphoma	0	0
Eastern Cooperative Oncology Group ECOG) Performance Status
ECOG performance status is used to describe a patient’s level of functioning in terms of their ability to care for themselves, daily activity, and physical ability (walking, working, etc.). The scale ranges from 0 to 5: • 0 = Fully active, no restrictions; • 1 = Restricted activity but ambulatory, able to carry out work of a light nature; • 2 = Ambulatory and capable of all self-care but unable to carry out work activities; • 3 = Limited self-care, confined to bed or chair more than 50% of waking hours; • 4 = Completely disabled, no selfcare, confined to bed or chair; • 5 = Dead
Units: Subjects
0 - Fully Active	2	8
1 - Restricted but ambulatory	2	2
2 - Ambulatory but unable to work	1	0
3 - Limited self-care	0	0

End points

Top of page

Reporting group title

Part 1 Arm A: DUR 1500 + LEN 20

Reporting group description

Reporting group title

Part 1 Arm A: DUR 1500 +LEN 20 +RIT 375

Reporting group description

Reporting group title

Part 1 Arm A: DUR 1500 +LEN 10 +RIT 375

Reporting group description

Reporting group title

Part 1 Arm B: DUR 1500 + IBR 420

Reporting group description

Reporting group title

Part 1 Arm B: DUR 1500 + IBR 560

Reporting group description

Reporting group title

Part 1 Arm C: DUR 1500 + RIT 375

Reporting group description

Reporting group title

Part 1 Arm C: DUR 1500 + BEN 70

Reporting group description

Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and bendamustine (BEN) 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.

Reporting group title

Part 1 Arm C: DUR 1500 +RIT 375 +BEN 70

Reporting group description

Reporting group title

Part 1 Arm C: DUR 1500 + RIT 375 + BEN 90

Reporting group description

Reporting group title

Part 2 Arm B CLL/SLL: DUR 1500 + IBR 420

Reporting group description

Reporting group title

Part 2 Arm B MCL: DUR 1500 + IBR 560

Reporting group description

Reporting group title

Part 2 Arm C FL: DUR 1500 + RIT 375 + BEN 70

Reporting group description

Reporting group title

Part 2 Arm C DLBCL: DUR 1500 + RIT 375 + BEN 70

Reporting group description

Reporting group title

Part 2 Arm C CLL/SLL:DUR 1500 +RIT 375 +BEN 70

Reporting group description

Reporting group title

Part 2 Arm D FL: DUR 1500

Reporting group description

Participants with follicular lymphoma received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Reporting group title

Part 2 Arm D DLBCL: DUR 1500

Reporting group description

Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Reporting group title

Part 2 Arm D CLL/SLL: DUR 1500

Reporting group description

Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Reporting group title

Part 2 Arm D MCL: DUR 1500

Reporting group description

Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Reporting group title

Part 2 Arm D HL: DUR 1500

Reporting group description

Participants with Hodgkin lymphoma (HL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Subject analysis set title

Part 1, Arm C: DUR 1500 mg + RIT 375 mg/mÂ² + BEN 90 mg/m²

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mG

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Part 2 Arm C DLBCL: DUR + RIT 375 mg/m² + BEN 70 mg/m²

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Arm A: Durvalumab + Lenalidomide ± Rituximab

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Arm B: Durvalumab + Ibrutinib

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Arm C: Durvalumab + Bendamustine ± Rituximab

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Arm D: Durvalumab Monotherapy

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants assigned to Arm D received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13.

Subject analysis set title

Arm D: Durvalumab Monotherapy

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants assigned to Arm D received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13.

Subject analysis set title

Arm A: Durvalumab + Lenalidomide Â± Rituximab

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Arm A: Lenalidomide 10 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Arm A: Lenalidomide 20 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Arm B: Ibrutinib 420 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Arm B: Ibrutinib 560 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Primary: Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)

Top of page

End point title

Part 1: Number of Participants with Dose Limiting Toxicities (DLTs) ^[1] ^[2]

End point description

Dose limiting toxicities were evaluated during the DLT evaluation period for participants in the dose finding cohorts. The severity grading was determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. A DLT is defined as below: Hematologic DLT • Grade 4 neutropenia observed for greater than 5 days duration • Grade 3 neutropenia associated with fever (≥ 38.5 °C) of any duration • Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or any requirement for platelets transfusion • Grade 4 anemia, unexplained by underlying disease • Any other grade 4 hematologic toxicity that does not resolve to participant's pretreatment baseline level within 72 hours. Non-Hematologic DLT • Any non-hematological toxicity ≥ Grade 3 except for alopecia and nausea controlled by medical management • Any treatment interruption greater than 2 weeks due to adverse event.

End point type

Primary

End point timeframe

Cycle 1 (28 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: Only summary statistics planned for this endpoint.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoints are cohort specific and do not report for all arms.

End point values	Part 1 Arm A: DUR 1500 + LEN 20	Part 1 Arm A: DUR 1500 +LEN 20 +RIT 375	Part 1 Arm A: DUR 1500 +LEN 10 +RIT 375	Part 1 Arm B: DUR 1500 + IBR 420	Part 1 Arm B: DUR 1500 + IBR 560	Part 1 Arm C: DUR 1500 + RIT 375	Part 1 Arm C: DUR 1500 + BEN 70	Part 1 Arm C: DUR 1500 +RIT 375 +BEN 70	Part 1 Arm C: DUR 1500 + RIT 375 + BEN 90
Number of subjects analysed	3	3	6	3	4	3	0 ^[3]	4	5
Units: Participants	0	3	1	0	0	0		0	1

Notes
[3] - Unable to calculate due to insufficient number of events.

No statistical analyses for this end point

Primary: Number of Participants with Treatment-emergent Adverse Events

Top of page

End point title

Number of Participants with Treatment-emergent Adverse Events ^[4]

End point description

Treatment-emergent adverse events (TEAEs) are defined as adverse events (AEs) occurring or worsening on or after the first dose of any study treatment (durvalumab, lenalidomide, ibrutinib, bendamustine or rituximab) and within 90 days after last dose of durvalumab or 28 days after the last dose of other study drugs, whichever was later, as well as those serious adverse events made known to the investigator at any time thereafter that were suspected of being related to study treatment. The intensity of AEs was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. For all other AEs not described in the CTCAE criteria, the intensity was assessed by the investigator as mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death (Grade 5).

End point type

Primary

End point timeframe

From first dose of any study drug to 90 days after last dose of durvalumab or 28 days after last dose of other study drugs, up to the data cut-off date of 6 March 2019. Maximum time on treatment was 55.4 weeks for DUR and 130 weeks for other study drugs.

Notes
[4] - 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 summary statistics planned for this endpoint.

End point values	Part 1 Arm A: DUR 1500 + LEN 20	Part 1 Arm A: DUR 1500 +LEN 20 +RIT 375	Part 1 Arm A: DUR 1500 +LEN 10 +RIT 375	Part 1 Arm B: DUR 1500 + IBR 420	Part 1 Arm B: DUR 1500 + IBR 560	Part 1 Arm C: DUR 1500 + RIT 375	Part 1 Arm C: DUR 1500 + BEN 70	Part 1 Arm C: DUR 1500 +RIT 375 +BEN 70	Part 1 Arm C: DUR 1500 + RIT 375 + BEN 90	Part 2 Arm B CLL/SLL: DUR 1500 + IBR 420	Part 2 Arm B MCL: DUR 1500 + IBR 560	Part 2 Arm C FL: DUR 1500 + RIT 375 + BEN 70	Part 2 Arm C DLBCL: DUR 1500 + RIT 375 + BEN 70	Part 2 Arm C CLL/SLL:DUR 1500 +RIT 375 +BEN 70	Part 2 Arm D FL: DUR 1500	Part 2 Arm D DLBCL: DUR 1500	Part 2 Arm D CLL/SLL: DUR 1500	Part 2 Arm D MCL: DUR 1500	Part 2 Arm D HL: DUR 1500
Number of subjects analysed	3	3	8	3	4	3	1	4	5	10	10	10	10	5	5	10	2	5	5
Units: Participants
Any TEAE	3	3	8	3	4	3	1	4	5	10	10	10	9	5	5	9	2	5	5
TEAE Related to Any Study Drug	3	3	8	3	4	3	0	4	5	10	9	10	9	5	4	3	0	3	2
CTCAE Grade 3-4 TEAE	1	3	7	2	3	2	1	3	4	8	10	6	9	5	4	7	1	4	3
CTCAE Grade 3-4 TEAE Related to Any Study Drug	1	3	7	1	1	2	0	2	2	7	6	5	7	3	3	2	0	1	1
CTCAE Grade 5 TEAE	0	0	0	0	0	0	0	0	0	0	1	0	0	1	1	4	0	0	0
CTCAE Grade 5 TEAE Related to Any Study Drug	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Serious TEAE	1	2	4	2	2	2	1	1	3	6	7	5	5	2	4	7	0	3	2
Serious TEAE Related to Any Study Drug	1	2	3	1	0	1	0	0	1	2	3	3	3	1	3	1	0	0	0
TEAE Leading to Discontinuation of Any Study Drug	1	0	3	1	0	0	0	0	0	0	2	2	1	2	1	0	0	1	0
TEAE Leading to Dose Modifications of Study Drug	1	3	3	3	4	3	1	4	4	8	9	7	4	3	2	0	0	3	3

No statistical analyses for this end point

Secondary: Overall Response Rate (ORR) During Durvalumab Treatment

Top of page

End point title

Overall Response Rate (ORR) During Durvalumab Treatment ^[5]

End point description

For lymphoma participants, response evaluation was based on International Working Group (IWG) response criteria for malignant lymphoma (the Lugano Classification). Overall response rate is defined as the percent of participants with best response of complete response (CR) or partial response (PR). For chronic lymphocytic leukemia participants, response evaluation was based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for diagnosis and treatment of CLL. The ORR is defined as the percent of participants with best response of CR, complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), PR, or partial response with lymphocytosis (PRL).

End point type

Secondary

End point timeframe

Up to 13 cycles (12 months)

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoints are cohort specific and do not report for all arms.

Part 1 Arm A: DUR 1500 + LEN 20

Part 1 Arm A: DUR 1500 +LEN 20 +RIT 375

Part 1 Arm A: DUR 1500 +LEN 10 +RIT 375

Part 1 Arm B: DUR 1500 + IBR 420

Part 1 Arm B: DUR 1500 + IBR 560

Part 1 Arm C: DUR 1500 + RIT 375

Part 1 Arm C: DUR 1500 + BEN 70

Part 1 Arm C: DUR 1500 +RIT 375 +BEN 70

Part 1 Arm C: DUR 1500 + RIT 375 + BEN 90

Part 2 Arm B CLL/SLL: DUR 1500 + IBR 420

Part 2 Arm B MCL: DUR 1500 + IBR 560

Part 2 Arm C FL: DUR 1500 + RIT 375 + BEN 70

Part 2 Arm C CLL/SLL:DUR 1500 +RIT 375 +BEN 70

Part 2 Arm D FL: DUR 1500

Part 2 Arm D DLBCL: DUR 1500

Part 2 Arm D CLL/SLL: DUR 1500

Part 2 Arm D MCL: DUR 1500

Part 2 Arm D HL: DUR 1500

Part 2 Arm C DLBCL: DUR + RIT 375 mg/m² + BEN 70 mg/m²

Number of subjects analysed

0 ^[6]

Units: percentage of participants

number (confidence interval 95%)

33.3 (0.8 to 90.6)

66.7 (9.4 to 99.2)

80.0 (28.4 to 99.5)

66.7 (9.4 to 99.2)

75.0 (19.4 to 99.4)

33.3 (0.8 to 90.6)

( to )

50.0 (6.8 to 93.2)

0 (-99999 to 99999)

88.9 (51.8 to 99.7)

60.0 (26.2 to 87.8)

88.9 (51.8 to 99.7)

50.0 (6.8 to 93.2)

0 (-99999 to 99999)

20.0 (0.5 to 71.6)

30.0 (6.7 to 65.2)

Notes
[6] - Unable to calculate due to insufficient number of events.

No statistical analyses for this end point

Secondary: Overall Response Rate During the Entire Study

Top of page

End point title

Overall Response Rate During the Entire Study

End point description

For lymphoma participants, response evaluation was based on International Working Group (IWG) response criteria for malignant lymphoma (the Lugano Classification) (Cheson, 2014). Overall response rate is defined as the percent of participants with best response of complete response (CR) or partial response (PR). For chronic lymphocytic leukemia participants, response evaluation was based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for diagnosis and treatment of CLL. The ORR is defined as the percentage of participants with best response of CR, complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), PR, or partial response with lymphocytosis (PRL). -99999/99999 = Not Available

End point type

Secondary

End point timeframe

From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.

Part 1 Arm A: DUR 1500 + LEN 20

Part 1 Arm A: DUR 1500 +LEN 20 +RIT 375

Part 1 Arm A: DUR 1500 +LEN 10 +RIT 375

Part 1 Arm B: DUR 1500 + IBR 420

Part 1 Arm B: DUR 1500 + IBR 560

Part 1 Arm C: DUR 1500 + RIT 375

Part 1 Arm C: DUR 1500 + BEN 70

Part 1 Arm C: DUR 1500 +RIT 375 +BEN 70

Part 1 Arm C: DUR 1500 + RIT 375 + BEN 90

Part 2 Arm B CLL/SLL: DUR 1500 + IBR 420

Part 2 Arm B MCL: DUR 1500 + IBR 560

Part 2 Arm C FL: DUR 1500 + RIT 375 + BEN 70

Part 2 Arm C DLBCL: DUR 1500 + RIT 375 + BEN 70

Part 2 Arm C CLL/SLL:DUR 1500 +RIT 375 +BEN 70

Part 2 Arm D FL: DUR 1500

Part 2 Arm D DLBCL: DUR 1500

Part 2 Arm D CLL/SLL: DUR 1500

Part 2 Arm D MCL: DUR 1500

Part 2 Arm D HL: DUR 1500

Number of subjects analysed

0 ^[7]

Units: percentage of participants

number (confidence interval 95%)

66.7 (9.4 to 99.2)

80.0 (28.4 to 99.5)

66.7 (9.4 to 99.2)

75.0 (19.4 to 99.4)

33.3 (0.8 to 90.6)

( to )

50.0 (6.8 to 93.2)

0 (-99999 to 99999)

100.0 (66.4 to 100.0)

70.0 (34.8 to 93.3)

88.9 (51.8 to 99.7)

30.0 (6.7 to 65.2)

50.0 (6.8 to 93.2)

0 (-99999 to 99999)

20.0 (0.5 to 71.6)

Notes
[7] - Unable to calculate due to insufficient number of events.

No statistical analyses for this end point

Secondary: Time to First Response

Top of page

End point title

Time to First Response

End point description

Time to response was calculated as the time from first dose of study drug to the first response date (CR or PR for lymphoma participants and CR, CRi, nPR, PR, or PRL for CLL participants).

End point type

Secondary

End point timeframe

From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.

Part 1 Arm A: DUR 1500 + LEN 20

Part 1 Arm A: DUR 1500 +LEN 20 +RIT 375

Part 1 Arm A: DUR 1500 +LEN 10 +RIT 375

Part 1 Arm B: DUR 1500 + IBR 420

Part 1 Arm B: DUR 1500 + IBR 560

Part 1 Arm C: DUR 1500 + RIT 375

Part 1 Arm C: DUR 1500 + BEN 70

Part 1 Arm C: DUR 1500 +RIT 375 +BEN 70

Part 1 Arm C: DUR 1500 + RIT 375 + BEN 90

Part 2 Arm B CLL/SLL: DUR 1500 + IBR 420

Part 2 Arm B MCL: DUR 1500 + IBR 560

Part 2 Arm C FL: DUR 1500 + RIT 375 + BEN 70

Part 2 Arm C DLBCL: DUR 1500 + RIT 375 + BEN 70

Part 2 Arm C CLL/SLL:DUR 1500 +RIT 375 +BEN 70

Part 2 Arm D FL: DUR 1500

Part 2 Arm D DLBCL: DUR 1500

Part 2 Arm D CLL/SLL: DUR 1500

Part 2 Arm D MCL: DUR 1500

Part 2 Arm D HL: DUR 1500

Number of subjects analysed

0 ^[8]

0 ^[9]

0 ^[10]

0 ^[11]

0 ^[12]

0 ^[13]

Units: weeks

median (full range (min-max))

70.85 (12.1 to 129.6)

12.60 (12.1 to 13.1)

18.20 (11.3 to 36.1)

11.85 (11.4 to 12.3)

13.40 (12.4 to 52.9)

13.00 (13.0 to 13.0)

( to )

13.10 (12.1 to 14.1)

( to )

12.10 (10.9 to 72.9)

12.10 (6.6 to 26.4)

12.35 (10.3 to 15.3)

12.00 (8.7 to 12.1)

12.10 (12.1 to 12.1)

( to )

13.10 (13.1 to 13.1)

Notes
[8] - Unable to calculate due to insufficient number of events.
[9] - Unable to calculate due to insufficient number of events.
[10] - Unable to calculate due to insufficient number of events.
[11] - Unable to calculate due to insufficient number of events.
[12] - Unable to calculate due to insufficient number of events.
[13] - Unable to calculate due to insufficient number of events.

No statistical analyses for this end point

Secondary: Kaplan-Meier Estimate of Duration of response

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End point title

Kaplan-Meier Estimate of Duration of response

End point description

Duration of response is defined for responders only as the time from the first documented response (CR or PR for lymphoma participants or CR, CRi, nPR, PR, or PRL for CLL participants) to disease progression or death (from any cause). For participants with response but no progression, or death, duration of response was censored at the last date that the participant was known to be progression-free. -99999/99999 = Not Available

End point type

Secondary

End point timeframe

From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.

Part 1 Arm A: DUR 1500 + LEN 20

Part 1 Arm A: DUR 1500 +LEN 20 +RIT 375

Part 1 Arm A: DUR 1500 +LEN 10 +RIT 375

Part 1 Arm B: DUR 1500 + IBR 420

Part 1 Arm B: DUR 1500 + IBR 560

Part 1 Arm C: DUR 1500 + RIT 375

Part 1 Arm C: DUR 1500 + BEN 70

Part 1 Arm C: DUR 1500 +RIT 375 +BEN 70

Part 1 Arm C: DUR 1500 + RIT 375 + BEN 90

Part 2 Arm B CLL/SLL: DUR 1500 + IBR 420

Part 2 Arm B MCL: DUR 1500 + IBR 560

Part 2 Arm C FL: DUR 1500 + RIT 375 + BEN 70

Part 2 Arm C DLBCL: DUR 1500 + RIT 375 + BEN 70

Part 2 Arm C CLL/SLL:DUR 1500 +RIT 375 +BEN 70

Part 2 Arm D FL: DUR 1500

Part 2 Arm D DLBCL: DUR 1500

Part 2 Arm D CLL/SLL: DUR 1500

Part 2 Arm D MCL: DUR 1500

Part 2 Arm D HL: DUR 1500

Number of subjects analysed

0 ^[14]

0 ^[15]

0 ^[16]

0 ^[17]

0 ^[18]

0 ^[19]

Units: weeks

median (confidence interval 95%)

10.14 (-99999 to 99999)

99999 (-99999 to 99999)

29.29 (-99999 to 99999)

( to )

99999 (-99999 to 99999)

( to )

99999 (-99999 to 99999)

24.14 (9.14 to 26.14)

99999 (-99999 to 99999)

( to )

11.14 (-99999 to 99999)

Notes
[14] - Unable to calculate due to insufficient number of events.
[15] - Unable to calculate due to insufficient number of events.
[16] - Unable to calculate due to insufficient number of events.
[17] - Unable to calculate due to insufficient number of events.
[18] - Unable to calculate due to insufficient number of events.
[19] - Unable to calculate due to insufficient number of events.

No statistical analyses for this end point

Secondary: Kaplan-Meier Estimate of Progression-free Survival (PFS)

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End point title

Kaplan-Meier Estimate of Progression-free Survival (PFS)

End point description

Progression-free survival was calculated as the time from first dose of study drug to the first documented progression or death (from any cause) during the entire efficacy evaluation period. For participants with no progression or death, PFS was censored at the last assessment date the participant was known to be progression-free. -99999/99999 = Not Available

End point type

Secondary

End point timeframe

From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.

Part 1 Arm A: DUR 1500 + LEN 20

Part 1 Arm A: DUR 1500 +LEN 20 +RIT 375

Part 1 Arm A: DUR 1500 +LEN 10 +RIT 375

Part 1 Arm B: DUR 1500 + IBR 420

Part 1 Arm B: DUR 1500 + IBR 560

Part 1 Arm C: DUR 1500 + RIT 375

Part 1 Arm C: DUR 1500 + BEN 70

Part 1 Arm C: DUR 1500 +RIT 375 +BEN 70

Part 1 Arm C: DUR 1500 + RIT 375 + BEN 90

Part 2 Arm B CLL/SLL: DUR 1500 + IBR 420

Part 2 Arm B MCL: DUR 1500 + IBR 560

Part 2 Arm C FL: DUR 1500 + RIT 375 + BEN 70

Part 2 Arm C DLBCL: DUR 1500 + RIT 375 + BEN 70

Part 2 Arm C CLL/SLL:DUR 1500 +RIT 375 +BEN 70

Part 2 Arm D FL: DUR 1500

Part 2 Arm D DLBCL: DUR 1500

Part 2 Arm D CLL/SLL: DUR 1500

Part 2 Arm D MCL: DUR 1500

Part 2 Arm D HL: DUR 1500

Number of subjects analysed

Units: months

median (confidence interval 95%)

8.41 (5.09 to 99999)

99999 (-99999 to 99999)

28.71 (4.50 to 99999)

9.69 (1.64 to 12.68)

1.25 (-99999 to 99999)

3.82 (1.25 to 99999)

2.48 (0.49 to 5.91)

99999 (-99999 to 99999)

14.65 (5.75 to 14.65)

2.06 (0.76 to 8.28)

99999 (-99999 to 99999)

1.68 (0.69 to 4.63)

1.17 (0.26 to 3.19)

2.76 (2.50 to 3.02)

2.33 (0.79 to 10.02)

2.66 (2.56 to 5.98)

No statistical analyses for this end point

Secondary: Time to Maximum Plasma Concentration (Tmax) of Durvalumab

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End point title

Time to Maximum Plasma Concentration (Tmax) of Durvalumab

End point description

End point type

Secondary

End point timeframe

Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.

End point values	Arm A: Durvalumab + Lenalidomide ± Rituximab	Arm B: Durvalumab + Ibrutinib	Arm C: Durvalumab + Bendamustine ± Rituximab	Arm D: Durvalumab Monotherapy
Number of subjects analysed	14	27	38	26
Units: days
median (full range (min-max))	0.0510 (0.042 to 1.035)	0.0479 (0.041 to 1.061)	0.0510 (0.042 to 6.788)	0.0420 (0.038 to 1.986)

No statistical analyses for this end point

Secondary: Maximum Observed Plasma Concentration (Cmax) of Durvalumab

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End point title

Maximum Observed Plasma Concentration (Cmax) of Durvalumab

End point description

End point type

Secondary

End point timeframe

Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.

End point values	Arm A: Durvalumab + Lenalidomide ± Rituximab	Arm B: Durvalumab + Ibrutinib	Arm C: Durvalumab + Bendamustine ± Rituximab	Arm D: Durvalumab Monotherapy
Number of subjects analysed	14	27	38	26
Units: μg/L
geometric mean (geometric coefficient of variation)	420264.066 ± 22.7	361906.229 ± 30.1	331572.478 ± 33.4	392663.668 ± 41.1

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration-time Curve From Time zero to Infinity (AUCinf) of Durvalumab

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End point title

Area Under the Plasma Concentration-time Curve From Time zero to Infinity (AUCinf) of Durvalumab

End point description

End point type

Secondary

End point timeframe

Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.

End point values	Arm A: Durvalumab + Lenalidomide ± Rituximab	Arm B: Durvalumab + Ibrutinib	Arm C: Durvalumab + Bendamustine ± Rituximab	Arm D: Durvalumab Monotherapy
Number of subjects analysed	14	27	38	25
Units: days*μg/L
geometric mean (geometric coefficient of variation)	4867431.378 ± 23.3	5818262.846 ± 42.1	4762968.345 ± 71.0	5593532.553 ± 53.0

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration-time Curve from Time Zero to the Last Measurable Concentration (AUClast) of Durvalumab

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End point title

Area Under the Plasma Concentration-time Curve from Time Zero to the Last Measurable Concentration (AUClast) of Durvalumab

End point description

End point type

Secondary

End point timeframe

Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.

End point values	Arm A: Durvalumab + Lenalidomide ± Rituximab	Arm B: Durvalumab + Ibrutinib	Arm C: Durvalumab + Bendamustine ± Rituximab	Arm D: Durvalumab Monotherapy
Number of subjects analysed	14	27	38	26
Units: days*μg/L
geometric mean (geometric coefficient of variation)	3120149.759 ± 29.5	3225869.344 ± 31.9	2670168.397 ± 46.7	3053060.746 ± 37.8

No statistical analyses for this end point

Secondary: Terminal Elimination Phase Half-Life (t½) of Durvalumab

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End point title

Terminal Elimination Phase Half-Life (t½) of Durvalumab

End point description

End point type

Secondary

End point timeframe

Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.

End point values	Arm B: Durvalumab + Ibrutinib	Arm C: Durvalumab + Bendamustine ± Rituximab	Arm D: Durvalumab Monotherapy	Arm A: Durvalumab + Lenalidomide Â± Rituximab
Number of subjects analysed	27	38	25	14
Units: days
geometric mean (geometric coefficient of variation)	17.344 ± 47.3	16.327 ± 57.4	15.399 ± 53.5	11.596 ± 46.6

No statistical analyses for this end point

Secondary: Clearance (CL) of Durvalumab

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End point title

Clearance (CL) of Durvalumab

End point description

End point type

Secondary

End point timeframe

Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.

End point values	Arm A: Durvalumab + Lenalidomide ± Rituximab	Arm B: Durvalumab + Ibrutinib	Arm C: Durvalumab + Bendamustine ± Rituximab	Arm D: Durvalumab Monotherapy
Number of subjects analysed	14	27	38	25
Units: L/day
geometric mean (geometric coefficient of variation)	0.3082 ± 23.3	0.2578 ± 42.1	0.3149 ± 71.0	0.2682 ± 53.0

No statistical analyses for this end point

Secondary: Volume of Distribution (Vz) of Durvalumab

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End point title

Volume of Distribution (Vz) of Durvalumab

End point description

End point type

Secondary

End point timeframe

Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.

End point values	Arm A: Durvalumab + Lenalidomide ± Rituximab	Arm B: Durvalumab + Ibrutinib	Arm C: Durvalumab + Bendamustine ± Rituximab	Arm D: Durvalumab Monotherapy
Number of subjects analysed	14	27	38	25
Units: liters
geometric mean (geometric coefficient of variation)	5.155 ± 41.9	6.451 ± 38.3	7.418 ± 33.7	5.957 ± 33.0

No statistical analyses for this end point

Secondary: Maximum Observed Plasma Concentration (Cmax) of Lenalidomide

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End point title

Maximum Observed Plasma Concentration (Cmax) of Lenalidomide

End point description

99999 = Not Available

End point type

Secondary

End point timeframe

Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.

End point values	Arm A: Lenalidomide 10 mg	Arm A: Lenalidomide 20 mg
Number of subjects analysed	5	4
Units: ng/mL
geometric mean (geometric coefficient of variation)
Cycle 1 Day 1	141.881 ± 22.0	309.917 ± 6.9
Cycle 1 Day 15	107.635 ± 40.9	174.090 ± 99999

No statistical analyses for this end point

Secondary: Time to Maximum Observed Plasma Concentration (Tmax) of Lenalidomide

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End point title

Time to Maximum Observed Plasma Concentration (Tmax) of Lenalidomide

End point description

End point type

Secondary

End point timeframe

Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.

End point values	Arm A: Lenalidomide 10 mg	Arm A: Lenalidomide 20 mg
Number of subjects analysed	5	4
Units: hours
median (full range (min-max))
Cycle 1 Day 1	1.9500 (1.000 to 3.917)	1.1667 (1.000 to 1.433)
Cycle 1 Day 15	3.0333 (1.233 to 4.000)	1.000 (1.000 to 1.000)

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration-time Curve from Time Zero to the Last Measurable Concentration (AUClast) of Lenalidomide

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End point title

Area Under the Plasma Concentration-time Curve from Time Zero to the Last Measurable Concentration (AUClast) of Lenalidomide

End point description

End point type

Secondary

End point timeframe

Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose

End point values	Arm A: Lenalidomide 10 mg	Arm A: Lenalidomide 20 mg
Number of subjects analysed	5	4
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	789.297 ± 84.3	805.299 ± 56.0

No statistical analyses for this end point

Secondary: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib

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End point title

Maximum Observed Plasma Concentration (Cmax) of Ibrutinib

End point description

End point type

Secondary

End point timeframe

Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.

End point values	Arm B: Ibrutinib 420 mg	Arm B: Ibrutinib 560 mg
Number of subjects analysed	13	13
Units: ng/mL
geometric mean (geometric coefficient of variation)
Cycle 1 Day 1	129.704 ± 98.0	67.728 ± 197.9
Cycle 1 Day 15	86.840 ± 136.9	72.436 ± 166.3

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration-time Curve from Time Zero to the Last Measurable Concentration (AUClast) of Ibrutinib

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End point title

Area Under the Plasma Concentration-time Curve from Time Zero to the Last Measurable Concentration (AUClast) of Ibrutinib

End point description

End point type

Secondary

End point timeframe

Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose

End point values	Arm B: Ibrutinib 420 mg	Arm B: Ibrutinib 560 mg
Number of subjects analysed	13	13
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	586.396 ± 117.2	436.855 ± 246.5

No statistical analyses for this end point

Secondary: Change from Baseline in Soluble Programmed Cell Death Ligand-1 (sPD-L1) Concentration

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End point title

Change from Baseline in Soluble Programmed Cell Death Ligand-1 (sPD-L1) Concentration

End point description

Change from baseline in sPD-L1 could not be calculated as all post-baseline samples were below the lower limit of quantification (<15.60 pg/mL).

End point type

Secondary

End point timeframe

Baseline (Cycle 1 Day 1 predose) and Day 1 of Cycles 2 to 13

Part 1 Arm A: DUR 1500 + LEN 20

Part 1 Arm A: DUR 1500 +LEN 20 +RIT 375

Part 1 Arm A: DUR 1500 +LEN 10 +RIT 375

Part 1 Arm B: DUR 1500 + IBR 420

Part 1 Arm B: DUR 1500 + IBR 560

Part 1 Arm C: DUR 1500 + RIT 375

Part 1 Arm C: DUR 1500 + BEN 70

Part 1 Arm C: DUR 1500 +RIT 375 +BEN 70

Part 1 Arm C: DUR 1500 + RIT 375 + BEN 90

Part 2 Arm B CLL/SLL: DUR 1500 + IBR 420

Part 2 Arm B MCL: DUR 1500 + IBR 560

Part 2 Arm C FL: DUR 1500 + RIT 375 + BEN 70

Part 2 Arm C DLBCL: DUR 1500 + RIT 375 + BEN 70

Part 2 Arm C CLL/SLL:DUR 1500 +RIT 375 +BEN 70

Part 2 Arm D FL: DUR 1500

Part 2 Arm D DLBCL: DUR 1500

Part 2 Arm D CLL/SLL: DUR 1500

Part 2 Arm D MCL: DUR 1500

Part 2 Arm D HL: DUR 1500

Number of subjects analysed

0 ^[20]

0 ^[21]

0 ^[22]

0 ^[23]

0 ^[24]

0 ^[25]

0 ^[26]

0 ^[27]

0 ^[28]

0 ^[29]

0 ^[30]

0 ^[31]

0 ^[32]

0 ^[33]

0 ^[34]

0 ^[35]

0 ^[36]

0 ^[37]

0 ^[38]

Units: pg/mL

arithmetic mean (standard deviation)

Notes
[20] - Unable to calculate due to insufficient number of events.
[21] - Unable to calculate due to insufficient number of events.
[22] - Unable to calculate due to insufficient number of events.
[23] - Unable to calculate due to insufficient number of events.
[24] - Unable to calculate due to insufficient number of events.
[25] - Unable to calculate due to insufficient number of events.
[26] - Unable to calculate due to insufficient number of events.
[27] - Unable to calculate due to insufficient number of events.
[28] - Unable to calculate due to insufficient number of events.
[29] - Unable to calculate due to insufficient number of events.
[30] - Unable to calculate due to insufficient number of events.
[31] - Unable to calculate due to insufficient number of events.
[32] - Unable to calculate due to insufficient number of events.
[33] - Unable to calculate due to insufficient number of events.
[34] - Unable to calculate due to insufficient number of events.
[35] - Unable to calculate due to insufficient number of events.
[36] - Unable to calculate due to insufficient number of events.
[37] - Unable to calculate due to insufficient number of events.
[38] - Unable to calculate due to insufficient number of events.

No statistical analyses for this end point

Secondary: Time to Maximum Observed Plasma Concentration (Tmax) of Ibrutinib

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End point title

Time to Maximum Observed Plasma Concentration (Tmax) of Ibrutinib

End point description

End point type

Secondary

End point timeframe

Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.

End point values	Arm B: Ibrutinib 420 mg	Arm B: Ibrutinib 560 mg
Number of subjects analysed	13	13
Units: hours
median (full range (min-max))
Cycle 1 Day 1	2.000 (0.000 to 4.367)	1.9333 (0.933 to 3.917)
Cycle 1 Day 15	1.8833 (1.000 to 4.000)	2.000 (1.000 to 4.083)

No statistical analyses for this end point

Post-hoc: Number of Participants with Treatment-emergent Adverse Events (TEAEs) - Extended Collection

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End point title

Number of Participants with Treatment-emergent Adverse Events (TEAEs) - Extended Collection

End point description

TEAEs defined as AEs occurring or worsening on or after first dose of any study treatment (durvalumab, lenalidomide, ibrutinib, bendamustine or rituximab) and within 90 days after last dose of durvalumab or 28 days after the last dose of other study drugs, whichever was later, as well as those serious adverse events made known to the investigator at any time thereafter that were suspected of being related to study treatment. Intensity of AEs graded according to the NCI CTCAE V. 4.03. For all other AEs not described in the CTCAE criteria, the intensity was assessed by investigator as mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death (Grade 5). This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date (assessments made until August 21, 2022).

End point type

Post-hoc

End point timeframe

From first dose of any study drug to 90 days after last dose of durvalumab or 28 days after last dose of other study drugs, up to the study completion date of August 21, 2022 (up to approximately 75 months).

End point values	Part 1 Arm A: DUR 1500 + LEN 20	Part 1 Arm A: DUR 1500 +LEN 20 +RIT 375	Part 1 Arm A: DUR 1500 +LEN 10 +RIT 375	Part 1 Arm B: DUR 1500 + IBR 420	Part 1 Arm B: DUR 1500 + IBR 560	Part 1 Arm C: DUR 1500 + RIT 375	Part 1 Arm C: DUR 1500 + BEN 70	Part 1 Arm C: DUR 1500 +RIT 375 +BEN 70	Part 1 Arm C: DUR 1500 + RIT 375 + BEN 90	Part 2 Arm B CLL/SLL: DUR 1500 + IBR 420	Part 2 Arm B MCL: DUR 1500 + IBR 560	Part 2 Arm C FL: DUR 1500 + RIT 375 + BEN 70	Part 2 Arm C DLBCL: DUR 1500 + RIT 375 + BEN 70	Part 2 Arm C CLL/SLL:DUR 1500 +RIT 375 +BEN 70	Part 2 Arm D FL: DUR 1500	Part 2 Arm D DLBCL: DUR 1500	Part 2 Arm D CLL/SLL: DUR 1500	Part 2 Arm D MCL: DUR 1500	Part 2 Arm D HL: DUR 1500
Number of subjects analysed	3	3	8	3	4	3	1	4	5	10	10	10	10	5	5	10	2	5	5
Units: Participants
Any TEAE	3	3	8	3	4	3	1	4	5	10	10	10	9	5	5	9	2	5	5
TEAE Related to Any Study Drug	3	3	8	3	4	3	0	4	5	10	9	10	9	5	4	3	0	3	2
CTCAE Grade 3-4 TEAE	1	3	7	2	4	2	1	3	4	9	10	6	9	5	4	7	1	4	3
CTCAE Grade 3-4 TEAE Related to Any Study Drug	1	3	7	1	1	2	0	2	2	8	6	5	7	3	3	2	0	1	1
CTCAE Grade 5 TEAE	0	0	0	0	0	0	0	0	0	0	1	0	0	1	1	4	0	0	0
CTCAE Grade 5 TEAE Related to Any Study Drug	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Serious TEAE	1	2	4	2	3	2	1	1	3	6	7	5	5	2	4	7	0	3	2
Serious TEAE Related to Any Study Drug	1	2	3	1	0	1	0	0	1	3	3	3	3	1	3	1	0	0	0
TEAE Leading to Discontinuation of Any Study Drug	1	0	3	1	0	0	0	0	0	0	2	2	1	2	1	0	0	1	0
TEAE Leading to Dose Modifications of Study Drug	1	3	5	3	4	3	1	4	4	9	9	7	4	3	2	0	0	3	3

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

SAEs and NSAEs assessed from first dose to 90 days from last dose of durva or 28 days from last dose of lenalidomide, ibrutinib, rituximab, bendamustine, or IFRT, whichever occurs later (up to approximately 75 months)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.0

Reporting group title

Part 1 Arm A: DUR 1500 + LEN 20 + RIT 375

Reporting group description

Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab (RIT) 375 mg/m² IV infusion on Days 2, 8, 15, and 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.

Reporting group title

Part 1 Arm A: DUR 1500 + LEN 20

Reporting group description

Reporting group title

Part 1 Arm C: DUR 1500 + RIT 375 + BEN 70

Reporting group description

Reporting group title

Part 1 Arm C: DUR 1500 + BEN 70

Reporting group description

Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and bendamustine (BEN) 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.

Reporting group title

Part 1 Arm C: DUR 1500 + RIT 375

Reporting group description

Reporting group title

Part 1 Arm B: DUR 1500 + IBR 560

Reporting group description

Reporting group title

Part 1 Arm B: DUR 1500 + IBR 420

Reporting group description

Reporting group title

Part 1 Arm A: DUR 1500 + LEN 10 + RIT 375

Reporting group description

Reporting group title

Part 2, Arm D CLL/SLL: DUR 1500 mg

Reporting group description

Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Reporting group title

Part 2, Arm D MCL: DUR 1500 mg

Reporting group description

Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Reporting group title

Part 2, Arm D DLBCL: DUR 1500 mg

Reporting group description

Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Reporting group title

Part 2 Arm D FL: DUR 1500

Reporting group description

Participants with follicular lymphoma received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Reporting group title

Part 2 Arm C CLL/SLL: DUR 1500 + RIT 375 + BEN 70

Reporting group description

Reporting group title

Part 2 Arm C DLBCL: DUR 1500 + RIT 375 + BEN 70

Reporting group description

Reporting group title

Part 2 Arm C FL: DUR 1500 + RIT 375 + BEN 70

Reporting group description

Reporting group title

Part 2 Arm B MCL: DUR 1500 + IBR 560

Reporting group description

Reporting group title

Part 2, Arm D HL: DUR 1500 mg

Reporting group description

Participants with Hodgkin lymphoma (HL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.

Reporting group title

Part 1 Arm C: DUR 1500 + RIT 375 + BEN 90

Reporting group description

Reporting group title

Part 2 Arm B CLL/SLL: DUR 1500 + IBR 420

Reporting group description

Part 1 Arm A: DUR 1500 + LEN 20 + RIT 375

Part 1 Arm A: DUR 1500 + LEN 20

Part 1 Arm C: DUR 1500 + RIT 375 + BEN 70

Part 1 Arm C: DUR 1500 + BEN 70

Part 1 Arm C: DUR 1500 + RIT 375

Part 1 Arm B: DUR 1500 + IBR 560

Part 1 Arm B: DUR 1500 + IBR 420

Part 1 Arm A: DUR 1500 + LEN 10 + RIT 375

Part 2, Arm D CLL/SLL: DUR 1500 mg

Part 2, Arm D MCL: DUR 1500 mg

Part 2, Arm D DLBCL: DUR 1500 mg

Part 2 Arm D FL: DUR 1500

Part 2 Arm C CLL/SLL: DUR 1500 + RIT 375 + BEN 70

Part 2 Arm C DLBCL: DUR 1500 + RIT 375 + BEN 70

Part 2 Arm C FL: DUR 1500 + RIT 375 + BEN 70

Part 2 Arm B MCL: DUR 1500 + IBR 560

Part 2, Arm D HL: DUR 1500 mg

Part 1 Arm C: DUR 1500 + RIT 375 + BEN 90

Part 2 Arm B CLL/SLL: DUR 1500 + IBR 420

Total subjects affected by serious adverse events

subjects affected / exposed

2 / 3 (66.67%)

1 / 3 (33.33%)

1 / 4 (25.00%)

1 / 1 (100.00%)

2 / 3 (66.67%)

3 / 4 (75.00%)

2 / 3 (66.67%)

4 / 8 (50.00%)

0 / 2 (0.00%)

4 / 5 (80.00%)

8 / 10 (80.00%)

4 / 5 (80.00%)

2 / 5 (40.00%)

5 / 10 (50.00%)

7 / 10 (70.00%)

2 / 5 (40.00%)

3 / 5 (60.00%)

6 / 10 (60.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Basal cell carcinoma

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

2 / 10 (20.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Prostate cancer

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 3 (33.33%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Squamous cell carcinoma of skin

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Squamous cell carcinoma of lung

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Vascular disorders

Jugular vein thrombosis

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypotension

subjects affected / exposed

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Superior vena cava syndrome

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 8 (12.50%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Asthenia

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General physical health deterioration

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

2 / 5 (40.00%)

2 / 10 (20.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malaise

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Generalised oedema

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

1 / 3 (33.33%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Multiple organ dysfunction syndrome

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Pyrexia

subjects affected / exposed

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

1 / 3 (33.33%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 8 (12.50%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 5 (20.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

2 / 5 (40.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

0 / 1

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Pain

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Immune system disorders

Cytokine release syndrome

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Dyspnoea

subjects affected / exposed

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

1 / 5 (20.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Organising pneumonia

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pleural effusion

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonitis

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

Electrocardiogram QT prolonged

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Alanine aminotransferase increased

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

2 / 10 (20.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

General physical condition abnormal

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Post procedural haemorrhage

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Acute coronary syndrome

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atrial fibrillation

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Cardiac failure

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Myocardial infarction

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Cerebral ischaemia

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 8 (12.50%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Syncope

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cytopenia

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Febrile neutropenia

subjects affected / exposed

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 8 (12.50%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Neutropenia

subjects affected / exposed

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pancytopenia

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Thrombocytopenia

subjects affected / exposed

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal pain

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Aptyalism

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal wall haematoma

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Diarrhoea

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

1 / 3 (33.33%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Colon dysplasia

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastric haemorrhage

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal perforation

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Haematemesis

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Rectal haemorrhage

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

1 / 3 (33.33%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small intestinal haemorrhage

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small intestinal obstruction

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Hepatitis

subjects affected / exposed

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyperbilirubinaemia

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

Drug reaction with eosinophilia and systemic symptoms

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 1 (100.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Endocrine disorders

Adrenal insufficiency

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Flank pain

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Bronchiolitis

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

1 / 3 (33.33%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchitis

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 8 (12.50%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchitis viral

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cellulitis

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Influenza

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lower respiratory tract infection

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lower respiratory tract infection viral

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lung infection

subjects affected / exposed

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 3 (33.33%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neutropenic sepsis

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Parainfluenzae virus infection

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pleural infection bacterial

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Septic shock

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sepsis

subjects affected / exposed

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 1 (100.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 8 (12.50%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

0 / 2

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Skin infection

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sinusitis

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Streptococcal infection

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 5 (20.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular device infection

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 10 (10.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Dehydration

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 8 (0.00%)

0 / 2 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyponatraemia

subjects affected / exposed

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 8 (12.50%)

0 / 2 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	Part 1 Arm A: DUR 1500 + LEN 20 + RIT 375	Part 1 Arm A: DUR 1500 + LEN 20	Part 1 Arm C: DUR 1500 + RIT 375 + BEN 70	Part 1 Arm C: DUR 1500 + BEN 70	Part 1 Arm C: DUR 1500 + RIT 375	Part 1 Arm B: DUR 1500 + IBR 560	Part 1 Arm B: DUR 1500 + IBR 420	Part 1 Arm A: DUR 1500 + LEN 10 + RIT 375	Part 2, Arm D CLL/SLL: DUR 1500 mg	Part 2, Arm D MCL: DUR 1500 mg	Part 2, Arm D DLBCL: DUR 1500 mg	Part 2 Arm D FL: DUR 1500	Part 2 Arm C CLL/SLL: DUR 1500 + RIT 375 + BEN 70	Part 2 Arm C DLBCL: DUR 1500 + RIT 375 + BEN 70	Part 2 Arm C FL: DUR 1500 + RIT 375 + BEN 70	Part 2 Arm B MCL: DUR 1500 + IBR 560	Part 2, Arm D HL: DUR 1500 mg	Part 1 Arm C: DUR 1500 + RIT 375 + BEN 90	Part 2 Arm B CLL/SLL: DUR 1500 + IBR 420
Total subjects affected by non serious adverse events
subjects affected / exposed	3 / 3 (100.00%)	3 / 3 (100.00%)	4 / 4 (100.00%)	1 / 1 (100.00%)	3 / 3 (100.00%)	4 / 4 (100.00%)	3 / 3 (100.00%)	8 / 8 (100.00%)	2 / 2 (100.00%)	5 / 5 (100.00%)	10 / 10 (100.00%)	5 / 5 (100.00%)	5 / 5 (100.00%)	9 / 10 (90.00%)	10 / 10 (100.00%)	10 / 10 (100.00%)	5 / 5 (100.00%)	5 / 5 (100.00%)	10 / 10 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Tumour flare
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Vascular disorders
Haematoma
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Hypertension
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	1	1	1	0	0	0	0	0	0	0	1	2	0	0	1
Venous thrombosis limb
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	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%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	2 / 5 (40.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	1	0	2	0	1	0	0	2	0	0
Aortic stenosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Embolism
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Deep vein thrombosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Axillary vein thrombosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Subclavian vein thrombosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Shock
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Embolism venous
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Venous thrombosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
General disorders and administration site conditions
Chills
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0	0	0	1	1	0	0	0	0	0	0
Asthenia
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	2 / 2 (100.00%)	3 / 5 (60.00%)	2 / 10 (20.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	3 / 10 (30.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	2 / 5 (40.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0	1	1	1	0	2	4	2	1	0	3	1	2	3	0	0
Influenza like illness
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	1	0	1	0	1	0	1	0	1
General physical health deterioration
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	2	0	0	0	1	0	0	0	0	0
Fatigue
subjects affected / exposed	2 / 3 (66.67%)	2 / 3 (66.67%)	1 / 4 (25.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	1 / 3 (33.33%)	2 / 8 (25.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	2 / 5 (40.00%)	3 / 10 (30.00%)	3 / 10 (30.00%)	2 / 10 (20.00%)	0 / 5 (0.00%)	2 / 5 (40.00%)	2 / 10 (20.00%)
occurrences all number	3	3	1	0	1	1	1	2	0	0	1	0	2	4	3	2	0	2	3
Early satiety
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Non-cardiac chest pain
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	1	0	1	0	0	0	0	0	1	0	1	0	0	0
Mucosal inflammation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Malaise
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	1	0
Pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 5 (40.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	3	0	2
Oedema peripheral
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	2 / 8 (25.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	2 / 5 (40.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	2 / 5 (40.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)
occurrences all number	0	0	1	0	0	1	0	2	0	0	1	3	0	0	1	1	2	1	1
Pyrexia
subjects affected / exposed	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 3 (0.00%)	2 / 8 (25.00%)	1 / 2 (50.00%)	4 / 5 (80.00%)	6 / 10 (60.00%)	2 / 5 (40.00%)	1 / 5 (20.00%)	4 / 10 (40.00%)	3 / 10 (30.00%)	2 / 10 (20.00%)	2 / 5 (40.00%)	3 / 5 (60.00%)	3 / 10 (30.00%)
occurrences all number	1	1	2	0	1	1	0	2	2	5	8	3	1	5	3	3	7	3	8
Discomfort
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Face oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Gravitational oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0
Inflammation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gait disturbance
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Feeling hot
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Injection site bruising
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Localised oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Nodule
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Peripheral swelling
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Pneumatosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Temperature intolerance
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Immunodeficiency
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Hypogammaglobulinaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Seasonal allergy
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Pelvic pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Penile oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Vaginal haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	1 / 3 (33.33%)	1 / 8 (12.50%)	0 / 2 (0.00%)	2 / 5 (40.00%)	1 / 10 (10.00%)	2 / 5 (40.00%)	1 / 5 (20.00%)	2 / 10 (20.00%)	4 / 10 (40.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	2 / 5 (40.00%)	3 / 10 (30.00%)
occurrences all number	0	1	0	0	1	1	1	1	0	2	1	2	1	3	4	1	1	2	5
Dyspnoea
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	2 / 4 (50.00%)	0 / 3 (0.00%)	3 / 8 (37.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	3 / 5 (60.00%)	2 / 5 (40.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0	1	4	0	4	0	0	3	3	3	2	1	0	1	0	0
Epistaxis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	0	0	0	1	0	0	0	0	2
Nasal congestion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	2	0	0	0	0	0	0	0	0	0	1	0
Oropharyngeal pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0	0	1	0	1	0	0	0	0	0	1	0	1	0	0	0
Laryngeal inflammation
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Hypoxia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	1	0	0
Pleural effusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	2 / 5 (40.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	3	0	1	0	0	0	1	0	0	0	1	0	2	0
Productive cough
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	1	0	0	1	1	0	0	0	0
Sinus congestion
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0
Sinus disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Sinus pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0
Tachypnoea
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Allergic cough
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Asthma
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Dysphonia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Hiccups
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dyspnoea exertional
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0
Interstitial lung disease
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Pleuritic pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Pharyngeal erythema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Nasal obstruction
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Nasal dryness
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Pneumonia aspiration
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Upper-airway cough syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Upper respiratory tract inflammation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Rales
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Pulmonary oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Wheezing
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	1	1	0	1	0	0	0
Apathy
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Confusional state
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	2 / 3 (66.67%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	1	0	0	0	0	0	0	0	0	0
Depression
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	2	0	0	1
Insomnia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	2 / 5 (40.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	2 / 5 (40.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	2	1	0	1	2	0	1
Cardiovascular somatic symptom disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	4	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Disorientation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Irritability
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Panic attack
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	0	0	0	0	2	0	1	0	0
Aspartate aminotransferase increased
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	1	0	0	0	2	1	1	1	0
Blood bilirubin increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	2 / 5 (40.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	2	0	0	1	1	0	1	0
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	0	0	2	1	1	0	0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Blood glucose increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Blood creatinine increased
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)
occurrences all number	1	0	1	0	0	1	0	0	0	0	0	0	1	1	0	1	1	0	2
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Immunoglobulins decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	2 / 5 (40.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0	0
Lymphocyte count decreased
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	3	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0
Lipase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Platelet count decreased
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	3	0	0	0	1	1	0	0	0	0	0	0	0	3	0	0	0	0
Weight decreased
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	3 / 5 (60.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	3	1	1	0	1	1	1	0	1	0
White blood cell count decreased
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	5	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0
Amylase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Blood calcium decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Blood uric acid increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0
Blood urine present
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Heart rate irregular
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Creatinine renal clearance increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
International normalised ratio increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Lymphocyte count increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Neutrophil count decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0
Monocyte count increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Streptococcus test positive
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Urine output decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Weight increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	2	0	0	2
Ligament sprain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	1
Infusion related reaction
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 8 (25.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0	1	0	0	3	0	0	0	0	0	2	1	0	0	1	0
Fall
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	2 / 5 (40.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	2	0	0	0	0	0	1	0	0	2
Overdose
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Wound
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Skin laceration
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Allergic transfusion reaction
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	2	0	0	0
Arthropod bite
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Eye contusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Humerus fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Joint dislocation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Procedural pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Neck injury
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Limb injury
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Joint injury
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Subdural haematoma
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Tooth fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Thermal burn
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Transfusion reaction
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Congenital, familial and genetic disorders
Epidermolysis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	3
Sinus tachycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	1	1	0	0	0	0
Pericardial disease
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Palpitations
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	1	0	0	0	0	0	0	2
Tachycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0
Supraventricular tachycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Sinus bradycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Nervous system disorders
Dysaesthesia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Dizziness
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0	0	1	1	0	0	1	1	0	1	0	0	1	0	2	0
Aphasia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Dysgeusia
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 8 (12.50%)	0 / 2 (0.00%)	2 / 5 (40.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	1	0	0	0	1	1	0	2	0	1	0	0	0	0	0	0	0
Peripheral sensory neuropathy
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	2	0	0	0	0	0	1	0	0	1	0	1	0	0	1	0	0	1
Paraesthesia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	1	1	0	0
Migraine
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Headache
subjects affected / exposed	2 / 3 (66.67%)	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	2 / 5 (40.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	3	1	2	0	0	2	1	0	0	1	1	0	1	2	1	1	2	0	0
Tremor
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	1	0	0	0	0	0	0
Amnesia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Depressed level of consciousness
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Hypoaesthesia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	1
Lethargy
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0
Memory impairment
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Sciatica
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Sensory disturbance
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Taste disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Syncope
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Somnolence
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 3 (0.00%)	2 / 3 (66.67%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	0 / 3 (0.00%)	3 / 8 (37.50%)	2 / 2 (100.00%)	1 / 5 (20.00%)	2 / 10 (20.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)	5 / 10 (50.00%)	1 / 10 (10.00%)	3 / 10 (30.00%)	2 / 5 (40.00%)	3 / 5 (60.00%)	0 / 10 (0.00%)
occurrences all number	0	2	1	0	0	4	0	4	3	7	4	1	9	6	1	4	2	4	0
Eosinophilia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0
Febrile neutropenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Haemolytic anaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	1 / 2 (50.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0
Leukopenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	3 / 8 (37.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	0 / 5 (0.00%)	2 / 5 (40.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	7	0	0	0	0	0	4	1	3	0	4	1
Lymphopenia
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 8 (25.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	2 / 5 (40.00%)	0 / 10 (0.00%)
occurrences all number	1	0	3	0	0	0	0	2	0	0	0	0	0	0	0	1	0	3	0
Neutropenia
subjects affected / exposed	1 / 3 (33.33%)	1 / 3 (33.33%)	2 / 4 (50.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	1 / 3 (33.33%)	4 / 8 (50.00%)	2 / 2 (100.00%)	3 / 5 (60.00%)	3 / 10 (30.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	3 / 10 (30.00%)	6 / 10 (60.00%)	3 / 10 (30.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)	4 / 10 (40.00%)
occurrences all number	4	3	4	0	2	1	1	9	5	8	5	0	1	5	7	6	1	3	14
Thrombocytopenia
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	0 / 3 (0.00%)	2 / 8 (25.00%)	2 / 2 (100.00%)	3 / 5 (60.00%)	4 / 10 (40.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)	6 / 10 (60.00%)	2 / 10 (20.00%)	3 / 10 (30.00%)	1 / 5 (20.00%)	2 / 5 (40.00%)	3 / 10 (30.00%)
occurrences all number	2	0	3	0	0	3	0	2	6	6	4	1	1	10	2	4	2	3	4
Pancytopenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Immune thrombocytopenic purpura
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Bone marrow failure
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Increased tendency to bruise
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1
Hypoacusis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Ear pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0
Ear discomfort
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vertigo
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	1	0	0	0	0	1	0	0	1
Eye disorders
Blepharitis
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Retinopathy hypertensive
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	1 / 2 (50.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Dry eye
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	1	0	0	1	0	0	0	0	0	0	1	1	0	1	0	0	1
Conjunctival haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	1 / 2 (50.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	1	0	0	1	0	0	1	0	0	0
Cataract
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	1 / 2 (50.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	1	0	0	1	0	1	0	0	2	0	0	0	0	1
Conjunctival oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Angle closure glaucoma
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctivitis allergic
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Eyelid disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Eyelid ptosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Iritis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Periorbital oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Vision blurred
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	1	0	0	0
Vitreous haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Vitreous floaters
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Vitreous detachment
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Visual impairment
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1
Abdominal distension
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1
Diarrhoea
subjects affected / exposed	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	2 / 4 (50.00%)	3 / 3 (100.00%)	2 / 8 (25.00%)	0 / 2 (0.00%)	2 / 5 (40.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	5 / 10 (50.00%)	3 / 5 (60.00%)	1 / 5 (20.00%)	5 / 10 (50.00%)
occurrences all number	1	2	1	0	1	5	5	2	0	3	0	1	2	2	3	6	3	2	11
Constipation
subjects affected / exposed	1 / 3 (33.33%)	3 / 3 (100.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	3 / 4 (75.00%)	0 / 3 (0.00%)	4 / 8 (50.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	2 / 5 (40.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	3 / 10 (30.00%)	2 / 10 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	3	7	1	0	1	3	0	4	0	0	0	2	1	1	3	2	0	0	1
Abdominal pain upper
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)
occurrences all number	1	0	1	0	0	3	0	2	0	1	1	1	0	0	0	0	0	0	2
Abdominal pain
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	2 / 4 (50.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	2 / 5 (40.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	2 / 5 (40.00%)	1 / 10 (10.00%)
occurrences all number	1	0	3	0	1	3	0	1	0	2	1	1	2	1	0	1	1	2	2
Dyspepsia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	1 / 2 (50.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	1	1	0	0	1	0	0	2
Dry mouth
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	1	0	0	0	1	1	0	0	0	0	1	0	1	0	1	1	0	1
Dysphagia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	2
Flatulence
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	1	0	1
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	0	0	1	0	0	1	2	0	0	1
Gingival pain
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Haemorrhoids
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Mouth ulceration
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0
Nausea
subjects affected / exposed	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	2 / 4 (50.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	3 / 5 (60.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	2 / 5 (40.00%)	3 / 10 (30.00%)	3 / 10 (30.00%)	2 / 10 (20.00%)	1 / 5 (20.00%)	2 / 5 (40.00%)	1 / 10 (10.00%)
occurrences all number	1	1	2	0	1	2	0	0	0	4	1	1	2	3	3	2	1	2	1
Rectal haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Oral pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Stomatitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	2	1	0	0
Vomiting
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 8 (12.50%)	0 / 2 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	1	1	1	0	4	2	1	0	1	1
Abdominal hernia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Anal fissure
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	1 / 2 (50.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Abdominal wall haematoma
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Ascites
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Dental caries
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Eructation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Haematemesis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Gastritis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Lip dry
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Oesophageal pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Lip haematoma
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Proctalgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Toothache
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	2	0	0	0
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hepatobiliary disorders
Hepatitis
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hepatocellular injury
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3
Hypertransaminasaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Cholestasis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Jaundice cholestatic
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Ocular icterus
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Skin and subcutaneous tissue disorders
Dermatitis exfoliative generalised
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Dermatitis acneiform
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0
Dry skin
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	2	0	2	0	0	1	1	1	0	0	0	0	0	0	0	1	0	0	0
Erythema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	3 / 10 (30.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	1	0	0	3
Ecchymosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	1
Hyperhidrosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	4	1	0	0	0	0	0	0	1	0	0	0	0	0
Night sweats
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Pruritus
subjects affected / exposed	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)
occurrences all number	1	1	0	0	0	2	0	1	0	1	1	0	1	2	1	0	1	1	1
Rash
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	2 / 4 (50.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	2 / 5 (40.00%)	1 / 5 (20.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	4 / 10 (40.00%)	2 / 5 (40.00%)	0 / 5 (0.00%)	4 / 10 (40.00%)
occurrences all number	0	0	0	0	1	4	1	0	0	0	1	2	2	2	0	4	2	0	4
Rash maculo-papular
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	2 / 8 (25.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	1	1	8	0	0	0	0	0	0	0	1	0	0	0
Skin fissures
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Skin lesion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	3	0	0	0	0	0	0	0	0	0	1	1	0	1
Urticaria
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	2	0	0	0	0	0	0	0	0	0	0	0	0
Alopecia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Decubitus ulcer
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Dermatitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Dermatitis contact
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Eczema asteatotic
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Onychoclasis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Neurodermatitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Hyperkeratosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Eczema nummular
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Petechiae
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Pruritus generalised
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Psoriasis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Purpura
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Rash generalised
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Rash macular
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	1	0	0
Rash pruritic
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Dysuria
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)
occurrences all number	1	0	0	0	0	0	1	0	0	1	0	0	0	0	1	1	0	0	2
Haematuria
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	3	0	0	0	0	0	0	0	0	0	2	0	0	0
Micturition urgency
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Renal failure
subjects affected / exposed	0 / 3 (0.00%)	2 / 3 (66.67%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	2	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Cystitis haemorrhagic
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Pollakiuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0
Renal colic
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Renal impairment
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0
Ureterolithiasis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Urinary tract pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Urinary incontinence
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	1	0	0	0	0	0	0	0	0	0
Hypothyroidism
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	2 / 8 (25.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	1	0	2	0	0	0	0	0	0	0	0	0	0	1
Thyroiditis
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	3 / 10 (30.00%)
occurrences all number	0	0	0	0	0	4	0	1	0	0	0	0	1	0	0	2	0	0	5
Back pain
subjects affected / exposed	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 5 (40.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)
occurrences all number	1	1	3	0	0	0	0	0	0	1	1	0	2	0	0	0	2	1	1
Bone pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	1	0	0
Groin pain
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Flank pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	1	0	1	1	0	0	0
Intervertebral disc degeneration
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Muscle discomfort
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Joint swelling
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Muscle spasms
subjects affected / exposed	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	1 / 3 (33.33%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	3 / 10 (30.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	3 / 10 (30.00%)
occurrences all number	1	1	0	0	0	3	2	1	0	0	0	0	0	0	0	3	0	0	3
Muscular weakness
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1
Musculoskeletal chest pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	1	0	0	0
Musculoskeletal discomfort
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	0	0	0	1	0	1	0	0	0
Pain in jaw
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Pain in extremity
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0
Myalgia
subjects affected / exposed	3 / 3 (100.00%)	2 / 3 (66.67%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)
occurrences all number	3	2	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	3
Neck pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Periarthritis
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Arthritis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Muscle mass
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Limb mass
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Joint noise
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Intervertebral disc disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Musculoskeletal stiffness
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Rotator cuff syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Synovial cyst
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Infections and infestations
Bronchiolitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Bronchitis
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	2 / 3 (66.67%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	3 / 10 (30.00%)
occurrences all number	1	0	0	0	4	1	1	0	0	0	0	0	0	1	2	2	0	0	6
Cystitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	2
Cytomegalovirus infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Folliculitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0
Gastroenteritis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0	0	1	0	0	0	1	0	0	0	0
Laryngitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Influenza
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1
Herpes zoster
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	2	0	0	0	0	0
Gastroenteritis viral
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Lip infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	1	0	1	0	0	1	0	1	0	1	0	0	1	0	1	0	2
Metapneumovirus infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Lung infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	3 / 10 (30.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	4
Lower respiratory tract infection
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	3	0	0	0	0	0	0	0	0	1	0	0	0	0	0	2	0	0	0
Oral candidiasis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	0	2	0	0	0	0
Otitis externa
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Paronychia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3
Pneumonia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	3	0	0	1	0	0	0	0	0	0	0	0	0
Respiratory tract infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	4
Oral fungal infection
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Sinusitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	1 / 2 (50.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	3	0	0	1	0	0	0	1	0	0	0	0	0	0
Rhinovirus infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	1	0
Rhinitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	1	0	0	0
Skin infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0
Tonsillitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0
Tooth infection
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	1	0	0	0	2	0	0	0	0	0	1	0	0	2	1	2	0	0
Urinary tract infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	1 / 3 (33.33%)	1 / 8 (12.50%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	3 / 10 (30.00%)
occurrences all number	0	0	1	0	2	4	1	1	0	1	0	0	0	0	0	0	0	0	3
Viral infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Ear infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Conjunctivitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1
Chronic sinusitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Bacterial sepsis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Herpes simplex
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Herpes virus infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Herpes ophthalmic
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Eye infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Hordeolum
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Enterocolitis infectious
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Pharyngitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Otitis media acute
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Otitis media
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Human herpesvirus 6 infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Pneumonia pseudomonal
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Stenotrophomonas sepsis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Sepsis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0
Pseudomonas infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Prostate infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Urinary tract infection viral
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Metabolism and nutrition disorders
Hyperglycaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	3	0	0	0	0	0	0	0	0	0	0	1	2	0	0	0	0
Dehydration
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	2 / 5 (40.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Decreased appetite
subjects affected / exposed	1 / 3 (33.33%)	2 / 3 (66.67%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 8 (25.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	2 / 10 (20.00%)	2 / 5 (40.00%)	1 / 5 (20.00%)	3 / 10 (30.00%)	2 / 10 (20.00%)	1 / 10 (10.00%)	2 / 5 (40.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)
occurrences all number	1	3	0	0	0	0	0	2	0	1	2	2	1	3	2	1	3	1	0
Hyperuricaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	2 / 10 (20.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	1	0	0	0	1	0	0	3	2	0	0	0	0	1	1	0	1
Hyperkalaemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	3	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0
Hypoalbuminaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	1	0	0
Hypocalcaemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	1 / 2 (50.00%)	2 / 5 (40.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	2	1	0	0	0	0	0	1	2	1	1	0	0	1	1	1	0	0
Hypokalaemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 8 (12.50%)	0 / 2 (0.00%)	3 / 5 (60.00%)	2 / 10 (20.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	5	0	0	0	0	0	1	0	3	2	3	0	1	0	4	1	0	1
Hypomagnesaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	2 / 5 (40.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	1	1	0	0	0	1	1	0	0
Hypophosphataemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Hypercalcaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Hyperlactacidaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Gout
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	4
Polydipsia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Hyponatraemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	3	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Hypoglycaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hypertriglyceridaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Tumour lysis syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 8 (0.00%)	0 / 2 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 10 (10.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0

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Were there any global substantial amendments to the protocol? Yes

04 May 2017

Addition of 2 new dose levels (ie, dose levels -2 and -3) to the Arm A dose finding part

14 Dec 2017

Discontinuation of Arm A to the enrollment of new participants

12 Sep 2019

Discontinuation of Follow-up Period, assessments and data collection

22 Apr 2020

Participants will move to a tablet formulation when the capsule formulation is no longer commercially available. For participants continuing on ibrutinib, scheduled clinic visits will be done according to standard of care per investigator’s discretion.

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.

Study placed on full clinical hold by US FDA on 05Sep2017. Study closed for further enrollment and subjects discontinued from all treatments. Subjects followed for SPMs for 5 years after last subject was enrolled per protocol

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Clinical trials

Clinical Trial Results: A Phase 1/2, Open-label, Multi-center Study to Assess the Safety and Tolerability of Durvalumab (Anti-PD-L1 Antibody) as Monotherapy and in Combination Therapy in Subjects With Lymphoma or Chronic Lymphocitic Leukemia

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)

Primary: Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)

Primary: Number of Participants with Treatment-emergent Adverse Events

Primary: Number of Participants with Treatment-emergent Adverse Events

Secondary: Overall Response Rate (ORR) During Durvalumab Treatment

Secondary: Overall Response Rate (ORR) During Durvalumab Treatment

Secondary: Overall Response Rate During the Entire Study

Secondary: Overall Response Rate During the Entire Study

Secondary: Time to First Response

Secondary: Time to First Response

Secondary: Kaplan-Meier Estimate of Duration of response

Secondary: Kaplan-Meier Estimate of Duration of response

Secondary: Kaplan-Meier Estimate of Progression-free Survival (PFS)

Secondary: Kaplan-Meier Estimate of Progression-free Survival (PFS)

Secondary: Time to Maximum Plasma Concentration (Tmax) of Durvalumab

Secondary: Time to Maximum Plasma Concentration (Tmax) of Durvalumab

Secondary: Maximum Observed Plasma Concentration (Cmax) of Durvalumab

Secondary: Maximum Observed Plasma Concentration (Cmax) of Durvalumab

Secondary: Area Under the Plasma Concentration-time Curve From Time zero to Infinity (AUCinf) of Durvalumab

Secondary: Area Under the Plasma Concentration-time Curve From Time zero to Infinity (AUCinf) of Durvalumab

Secondary: Area Under the Plasma Concentration-time Curve from Time Zero to the Last Measurable Concentration (AUClast) of Durvalumab

Secondary: Area Under the Plasma Concentration-time Curve from Time Zero to the Last Measurable Concentration (AUClast) of Durvalumab

Secondary: Terminal Elimination Phase Half-Life (t½) of Durvalumab

Secondary: Terminal Elimination Phase Half-Life (t½) of Durvalumab

Secondary: Clearance (CL) of Durvalumab

Secondary: Clearance (CL) of Durvalumab

Secondary: Volume of Distribution (Vz) of Durvalumab

Secondary: Volume of Distribution (Vz) of Durvalumab

Secondary: Maximum Observed Plasma Concentration (Cmax) of Lenalidomide

Secondary: Maximum Observed Plasma Concentration (Cmax) of Lenalidomide

Secondary: Time to Maximum Observed Plasma Concentration (Tmax) of Lenalidomide

Secondary: Time to Maximum Observed Plasma Concentration (Tmax) of Lenalidomide

Secondary: Area Under the Plasma Concentration-time Curve from Time Zero to the Last Measurable Concentration (AUClast) of Lenalidomide

Secondary: Area Under the Plasma Concentration-time Curve from Time Zero to the Last Measurable Concentration (AUClast) of Lenalidomide

Secondary: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib

Secondary: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib

Secondary: Area Under the Plasma Concentration-time Curve from Time Zero to the Last Measurable Concentration (AUClast) of Ibrutinib

Secondary: Area Under the Plasma Concentration-time Curve from Time Zero to the Last Measurable Concentration (AUClast) of Ibrutinib

Secondary: Change from Baseline in Soluble Programmed Cell Death Ligand-1 (sPD-L1) Concentration

Secondary: Change from Baseline in Soluble Programmed Cell Death Ligand-1 (sPD-L1) Concentration

Secondary: Time to Maximum Observed Plasma Concentration (Tmax) of Ibrutinib

Secondary: Time to Maximum Observed Plasma Concentration (Tmax) of Ibrutinib

Post-hoc: Number of Participants with Treatment-emergent Adverse Events (TEAEs) - Extended Collection

Post-hoc: Number of Participants with Treatment-emergent Adverse Events (TEAEs) - Extended Collection

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 1/2, Open-label, Multi-center Study to Assess the Safety and Tolerability of Durvalumab (Anti-PD-L1 Antibody) as Monotherapy and in Combination Therapy in Subjects With Lymphoma or Chronic Lymphocitic Leukemia