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Clinical Trial Results:
A Phase 1/2a Study of BMS-986178 Administered Alone or in Combination with Nivolumab and/or Ipilimumab in Subjects with Advanced Solid Tumors

Summary
EudraCT number	2015-004816-39
Trial protocol	ES NL IT
Global end of trial date	02 Nov 2020

Results information
Results version number	v1(current)
This version publication date	18 Nov 2021
First version publication date	18 Nov 2021
Other versions

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

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Trial information

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Sponsor protocol code

CA012-004

ISRCTN number

US NCT number

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

01 Sep 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

02 Nov 2020

Was the trial ended prematurely?

Main objective of the trial

The primary objective is to determine the safety, tolerability, dose-limiting toxicities (DLTs), and maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of BMS-986178 administered alone or in combination with nivolumab and/or ipilimumab in subjects with advanced solid tumors.

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

17 Jun 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 68

Country: Number of subjects enrolled

Canada: 27

Country: Number of subjects enrolled

Israel: 2

Country: Number of subjects enrolled

Italy: 2

Country: Number of subjects enrolled

Netherlands: 17

Country: Number of subjects enrolled

Spain: 50

Worldwide total number of subjects

166

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)

100

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

165 participants were randomized and treated in Parts 1-8. 1 Participant was randomized and treated in Part 9 Cohort 1. Parts 2B, 2D, 2E, 3B, 3C, and Part 9 Cohort 2 did not enroll any participants.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part 1: BMS 20 mg Q2W

Arm description

Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles.

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

20 mg - The administration of the entire bag or syringe (if syringe pump is used) contents should be infused over approximately 30 minutes (including a flush up to 20 mL to completely flush the infusion line), through an IV infusion set

Part 1: BMS 40 mg Q2W

Arm description

Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles.

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

40 mg - The administration of the entire bag or syringe (if syringe pump is used) contents should be infused over approximately 30 minutes (including a flush up to 20 mL to completely flush the infusion line), through an IV infusion set

Part 1: BMS 80 mg Q2W

Arm description

Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles.

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

80 mg - The administration of the entire bag or syringe (if syringe pump is used) contents should be infused over approximately 30 minutes (including a flush up to 20 mL to completely flush the infusion line), through an IV infusion set

Part 1: BMS 160 mg Q2W

Arm description

Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles.

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

160 mg - The administration of the entire bag or syringe (if syringe pump is used) contents should be infused over approximately 30 minutes (including a flush up to 20 mL to completely flush the infusion line), through an IV infusion set

Part 1: BMS 320 mg Q2W

Arm description

Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles.

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

320 mg - The administration of the entire bag or syringe (if syringe pump is used) contents should be infused over approximately 30 minutes (including a flush up to 20 mL to completely flush the infusion line), through an IV infusion set

Part 2 BMS 20 mg + Nivo 240 mg Q2W

Arm description

Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles.

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

240 mg - Administered as a flat dose

Part 2: BMS 40 mg + Nivo 240 mg Q2W

Arm description

Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles.

Arm type

Experimental

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

240 mg - Administered as a flat dose

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Part 2: BMS 80 mg + Nivo 240 mg Q2W

Arm description

Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles.

Arm type

Experimental

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

240 mg - Administered as a flat dose

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Part 2: BMS 160 mg + Nivo 240 mg Q2W

Arm description

Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles.

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

240 mg - Administered as a flat dose

Part 2: BMS 320 mg + Nivo 240 mg Q2W

Arm description

Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles.

Arm type

Experimental

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

240 mg - Administered as a flat dose

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W

Arm description

Each treatment cycle will be 3 weeks in length. BMS-986178 20mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles.

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Ipilimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

1 mg/kg

Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W

Arm description

Each treatment cycle will be 3 weeks in length. BMS-986178 40mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles.

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Ipilimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

1 mg/kg

Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W

Arm description

Each treatment cycle will be 3 weeks in length. BMS-986178 80mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles.

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Ipilimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

1 mg/kg

Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W

Arm description

Each treatment cycle will be 3 weeks in length. BMS-986178 160mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles.

Arm type

Experimental

Investigational medicinal product name

Ipilimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

1 mg/kg

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W

Arm description

Each treatment cycle will be 3 weeks in length. BMS-986178 320mg will be administered q3w starting on Cycle 1 Day 1, up to and including 8 cycles. Ipilimumab will be administered at a dose of 1 mg/kg q3w starting on Day 1 for 4 cycles. Only BMS-986178 will be administered in the last 4 cycles.

Arm type

Experimental

Investigational medicinal product name

Ipilimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

1 mg/kg

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)

Arm description

Participants with bladder cancer receive BMS-986178 (80 mg) and Nivolumab administered at a flat dose of 240 mg. Each treatment cycle will be 2 weeks in length and study drugs will be administered every 2 weeks starting on Day 1 of each cycle for up to 12 cycles.

Arm type

Experimental

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

240 mg - Administered as a flat dose

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Part 4: BMS 80 mg + Nivo 480mg Q4W

Arm description

Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w).

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

480 mg - Administered as a flat dose

Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W

Arm description

Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy).

Arm type

Experimental

Investigational medicinal product name

Ipilimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

3 mg/kg

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W

Arm description

Participants with renal cell carcinoma (RCC) recieve BMS-986178 (40mg) administered at a flat dose in combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4, followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 (40 mg) and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle.

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Ipilimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

1 mg/kg

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

240 mg - Administered as a flat dose

Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W

Arm description

Participants with renal cell carcinoma (RCC) receive BMS-986178 (40mg) administered combination with nivolumab (240 mg) and ipilimumab (1 mg/kg) every 3 weeks (q3w) during Cycles 1 to 4 followed by maintenance therapy (Cycle 5 and beyond) in which BMS-986178 and nivolumab (480 mg) will be administered every 4 weeks (q4w). Study drugs will be administered accordingly starting on Day 1 of each cycle.

Arm type

Experimental

Investigational medicinal product name

Ipilimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

1 mg/kg

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W

Arm description

BMS-986178 will be administered at a flat dose of 40 mg (q2w) in combination with nivolumab (240 mg; q2w) and ipilimumab (1 mg/kg; q6w) for four 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle. If participants continue for additional cycles, past cycle 4, all study drugs (BMS-986178/nivolumab/ipilimumab) will continue for all cycles.

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Ipilimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

1 mg/kg

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

240 mg - Administered as a flat dose

Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W

Arm description

Participants with non-small cell lung cancer (NSCLC) receive BMS-986178 (40 mg) in combination with nivolumab 240 mg every 2 weeks (q2w) and ipilimumab 1 mg/kg every 6 weeks (q6w) for four, 6-week cycles. Study drugs will be administered accordingly starting on Day 1 of each cycle.

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

240 mg - Administered as a flat dose

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

240 mg - Administered as a flat dose

Investigational medicinal product name

Ipilimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

1 mg/kg

Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W

Arm description

BMS-986178 (20 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178.

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

480 mg - Administered as a flat dose

Investigational medicinal product name

Tetanus vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intradermal use

Dosage and administration details

Tdap preferred, Td or equivalent administered first on Cycle 1 Day 1 prior to administration of other study treatments

Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W

Arm description

BMS-986178 (40 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178.

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

480 mg - Administered as a flat dose

Investigational medicinal product name

Tetanus vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intradermal use

Dosage and administration details

Tdap preferred, Td or equivalent administered first on Cycle 1 Day 1 prior to administration of other study treatments

Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W

Arm description

BMS-986178 (80 mg) will be administered as a flat dose every 12 weeks (q12w) in combination with nivolumab flat dose (480 mg) every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length starting on Day 1 of each cycle. There will be up to 9 cycles, to allow for 24 months of treatment. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab and BMS-986178.

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Tetanus vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intradermal use

Dosage and administration details

Tdap preferred, Td or equivalent administered first on Cycle 1 Day 1 prior to administration of other study treatments

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

480 mg - Administered as a flat dose

Part 8: Cohort 4- Nivo 480 mg Q4W

Arm description

Nivolumab monotherapy will be administered as a flat dose of 480 mg every 4 weeks (q4w). Each treatment cycle will be 12 weeks in length and will be dosed for up to 9 cycles, 24 months of dosing. Treatment will be given on Day 1, Day 29 and 57 of each cycle. A tetanus vaccine (Tdap preferred, Td or equivalent after discussion with the medical monitor) will be administered first on Cycle 1 Day 1 prior to administration of nivolumab monotherapy.

Arm type

Experimental

Investigational medicinal product name

Tetanus vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intradermal use

Dosage and administration details

Tdap preferred, Td or equivalent administered first on Cycle 1 Day 1 prior to administration of other study treatments

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

480 mg - Administered as a flat dose

Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine

Arm description

Cohort 1: Cyclophosphamide 300 mg/m2 was administered 3 days prior to C1D1. DPV-001 1 mg was given on C1D1 intranodal then intradermal on C1D8, C1D15, C2D1, C2D15, C3D1, C4D1, C5D1, C6D1, C9D1 and C12D1. Nivolumab 240 mg was administered on C1D15 followed by nivolumab 480 mg was Q4W on day 1 of cycles 2-26. BMS-986178 40 mg infusion was administered on day 1 of cycles 1-6, 9, and 12. Each treatment cycle is 4 weeks and there are up to 26 cycles.

Arm type

Experimental

Investigational medicinal product name

BMS-986178

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

480 mg - Administered as a flat dose

Investigational medicinal product name

DPV-001 (UbiLT3 and UbiLT6)

Investigational medicinal product code

Other name

DRibbles Vaccine

Pharmaceutical forms

Injection

Routes of administration

Other use

Dosage and administration details

0.5 mL UbiLT3 into 1 lymph node and 0.5 mL of UbiLT6 into another lymph node - administered intranodal under ultrasound guidance.

Investigational medicinal product name

DPV-001 (UbiLT3 and UbiLT6)

Investigational medicinal product code

Other name

DRibbles Vaccine

Pharmaceutical forms

Injection

Routes of administration

Intradermal use

Dosage and administration details

1 mg - can alternate between either UbiLT3 or UbiLT6

Number of subjects in period 1	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Started	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	1
Completed	3	4	4	3	3	4	8	10	7	8	3	6	5	6	5	15	10	2	5	1	4	8	2	1	1	1	0
Not completed	1	0	0	1	1	3	0	2	1	0	1	4	2	2	1	3	2	4	2	0	2	1	0	1	1	1	1
Adverse event, serious fatal	1	-	-	1	-	-	-	2	-	-	-	4	2	2	-	2	2	2	1	-	-	-	-	-	-	-	-
Participant withdrew consent	-	-	-	-	-	2	-	-	-	-	-	-	-	-	1	-	-	2	1	-	2	-	-	-	-	-	-
Other reasons	-	-	-	-	1	1	-	-	1	-	1	-	-	-	-	-	-	-	-	-	-	1	-	1	1	1	-
Lost to follow-up	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	1	-	-	-	-	-	-	-	-	-	-	-
Disease Progression	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	1

Baseline characteristics

Top of page

Reporting group title

Part 1: BMS 20 mg Q2W

Reporting group description

Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles.

Reporting group title

Part 1: BMS 40 mg Q2W

Reporting group description

Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles.

Reporting group title

Part 1: BMS 80 mg Q2W

Reporting group description

Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles.

Reporting group title

Part 1: BMS 160 mg Q2W

Reporting group description

Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles.

Reporting group title

Part 1: BMS 320 mg Q2W

Reporting group description

Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles.

Reporting group title

Part 2 BMS 20 mg + Nivo 240 mg Q2W

Reporting group description

Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles.

Reporting group title

Part 2: BMS 40 mg + Nivo 240 mg Q2W

Reporting group description

Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles.

Reporting group title

Part 2: BMS 80 mg + Nivo 240 mg Q2W

Reporting group description

Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles.

Reporting group title

Part 2: BMS 160 mg + Nivo 240 mg Q2W

Reporting group description

Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles.

Reporting group title

Part 2: BMS 320 mg + Nivo 240 mg Q2W

Reporting group description

Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles.

Reporting group title

Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W

Reporting group description

Reporting group title

Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W

Reporting group description

Reporting group title

Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W

Reporting group description

Reporting group title

Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W

Reporting group description

Reporting group title

Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W

Reporting group description

Reporting group title

Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)

Reporting group description

Reporting group title

Part 4: BMS 80 mg + Nivo 480mg Q4W

Reporting group description

Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w).

Reporting group title

Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W

Reporting group description

Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy).

Reporting group title

Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W

Reporting group description

Reporting group title

Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W

Reporting group description

Reporting group title

Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W

Reporting group description

Reporting group title

Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W

Reporting group description

Reporting group title

Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W

Reporting group description

Reporting group title

Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W

Reporting group description

Reporting group title

Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W

Reporting group description

Reporting group title

Part 8: Cohort 4- Nivo 480 mg Q4W

Reporting group description

Reporting group title

Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine

Reporting group description

Reporting group values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine	Total
Number of subjects	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	1	166
Age Categorical
Units: Participants
<=18 years	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Between 18 and 65 years	4	1	2	1	3	5	3	10	5	5	3	7	4	7	4	8	8	5	7	0	2	2	2	1	0	0	1	100
>=65 years	0	3	2	3	1	2	5	2	3	3	1	3	3	1	2	10	4	1	0	1	4	7	0	1	2	2	0	66
Age continuous
Units: years
arithmetic mean (standard deviation)	43.5 ( 16.8 )	68.5 ( 10.8 )	53.5 ( 18.9 )	60.0 ( 16.2 )	55.0 ( 14.0 )	58.4 ( 6.8 )	66.8 ( 10.2 )	55.0 ( 10.3 )	59.1 ( 12.3 )	61.1 ( 7.3 )	56.5 ( 13.2 )	59.5 ( 8.7 )	60.3 ( 12.7 )	47.4 ( 13.7 )	56.7 ( 10.8 )	65.8 ( 7.7 )	56.8 ( 11.1 )	54.3 ( 15.6 )	52.0 ( 12.2 )	71.0 ( 99999 )	65.3 ( 7.9 )	69.7 ( 8.3 )	62.0 ( 2.8 )	66.5 ( 7.8 )	71.0 ( 5.7 )	75.0 ( 5.7 )	51.0 ( 99999 )	-
Sex: Female, Male
Units: Participants
Female	1	1	3	1	1	3	6	3	6	2	3	5	4	7	2	1	8	3	2	0	2	0	0	1	1	0	1	67
Male	3	3	1	3	3	4	2	9	2	6	1	5	3	1	4	17	4	3	5	1	4	9	2	1	1	2	0	99
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Asian	0	1	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	4
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	0	0	0	0	0	0	0	0
Black or African American	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	4
White	2	3	4	4	3	6	8	12	8	8	4	8	7	7	6	18	11	6	7	1	5	8	2	2	2	2	1	155
More than one race	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	1	0	0	0	0	1	0	1	0	0	0	0	2	0	0	0	0	0	1	0	0	0	0	0	0	0	0	6
Not Hispanic or Latino	3	4	4	3	2	6	6	5	3	3	2	7	4	4	5	6	5	3	0	1	4	3	1	2	1	1	1	89
Unknown or Not Reported	0	0	0	1	2	0	2	6	5	5	2	3	1	4	1	12	7	3	6	0	2	6	1	0	1	1	0	71

End points

Top of page

Reporting group title

Part 1: BMS 20 mg Q2W

Reporting group description

Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 20mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles.

Reporting group title

Part 1: BMS 40 mg Q2W

Reporting group description

Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 40mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles.

Reporting group title

Part 1: BMS 80 mg Q2W

Reporting group description

Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 80mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles.

Reporting group title

Part 1: BMS 160 mg Q2W

Reporting group description

Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 160mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles.

Reporting group title

Part 1: BMS 320 mg Q2W

Reporting group description

Part 1A is BMS-986178 monotherapy dose escalation. Dosing of BMS-986178 320mg will begin on Day 1 of each cycle and will be administered every 2 week (q2w) for up to 12 cycles.

Reporting group title

Part 2 BMS 20 mg + Nivo 240 mg Q2W

Reporting group description

Dosing of BMS-986178 20mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles.

Reporting group title

Part 2: BMS 40 mg + Nivo 240 mg Q2W

Reporting group description

Dosing of BMS-986178 40mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles.

Reporting group title

Part 2: BMS 80 mg + Nivo 240 mg Q2W

Reporting group description

Dosing of BMS-986178 80mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles.

Reporting group title

Part 2: BMS 160 mg + Nivo 240 mg Q2W

Reporting group description

Dosing of BMS-986178 160mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles.

Reporting group title

Part 2: BMS 320 mg + Nivo 240 mg Q2W

Reporting group description

Dosing of BMS-986178 320mg and Nivolumab flat dose of 240 mg will be administered every 2 weeks (q2w) starting on Day 1 of each cycle for up to 12 cycles.

Reporting group title

Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W

Reporting group description

Reporting group title

Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W

Reporting group description

Reporting group title

Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W

Reporting group description

Reporting group title

Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W

Reporting group description

Reporting group title

Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W

Reporting group description

Reporting group title

Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)

Reporting group description

Reporting group title

Part 4: BMS 80 mg + Nivo 480mg Q4W

Reporting group description

Combination arm of BMS-986178 (80 mg) with nivolumab (480 mg) to be administered every 4 weeks (q4w).

Reporting group title

Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W

Reporting group description

Combination arm of BMS-986178 (80 mg) with Ipilimumab 3 mg/kg administered every 3 weeks (q3w) for 4 doses, followed by monotherapy with BMS-986178 (maintenance therapy).

Reporting group title

Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W

Reporting group description

Reporting group title

Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W

Reporting group description

Reporting group title

Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W

Reporting group description

Reporting group title

Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W

Reporting group description

Reporting group title

Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W

Reporting group description

Reporting group title

Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W

Reporting group description

Reporting group title

Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W

Reporting group description

Reporting group title

Part 8: Cohort 4- Nivo 480 mg Q4W

Reporting group description

Reporting group title

Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine

Reporting group description

Primary: The number of Participants Experiencing Adverse Events (AEs)

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End point title

The number of Participants Experiencing Adverse Events (AEs) ^[1]

End point description

The number of participants experiencing adverse events (AEs) to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.

End point type

Primary

End point timeframe

From first dose to 100 days after last dose (up to approximately 2.5 years)

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 were planned for these endpoints

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	1
Units: Participants	4	4	4	3	4	7	8	12	7	8	4	10	7	8	6	18	12	6	6	1	6	9	2	2	2	2	1

No statistical analyses for this end point

Primary: The Number of Participants Experiencing Serious Adverse Events (SAEs)

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End point title

The Number of Participants Experiencing Serious Adverse Events (SAEs) ^[2]

End point description

The number of participants experiencing serious adverse events (SAEs) to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. A SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and/or is an important medical event.

End point type

Primary

End point timeframe

From first dose to 100 days after last dose (up to approximately 2.5 years)

Notes
[2] - 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 were planned for these endpoints

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	1
Units: Participants	3	4	2	3	3	3	6	7	4	5	2	6	6	5	2	11	7	4	4	1	6	5	0	1	1	1	1

No statistical analyses for this end point

Primary: The Number of Participants with Clinical Laboratory Test Abnormalities (Hematology)

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End point title

The Number of Participants with Clinical Laboratory Test Abnormalities (Hematology) ^[3]

End point description

The number of participants with clinical laboratory test abnormalities to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. Baseline is defined as the last non-missing measurement prior to the first dosing date and time

End point type

Primary

End point timeframe

From baseline to 100 days after last dose (up to approximately 2.5 years)

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only summary statistics were planned for these endpoints

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	1
Units: Participants
HEMOGLOBIN GRADE 1	2	0	4	1	2	1	4	3	3	6	3	4	2	5	1	9	4	1	3	1	2	7	1	1	1	1	1
HEMOGLOBIN GRADE 2	1	2	0	2	1	4	2	5	2	0	1	6	3	1	4	6	5	2	2	0	2	2	1	0	1	0	0
HEMOGLOBIN GRADE 3	1	1	0	1	0	1	1	1	2	1	0	0	1	2	1	3	1	2	0	0	1	0	0	1	0	1	0
PLATELET COUNT GRADE 1	1	1	1	1	0	1	2	1	1	0	0	1	2	1	2	4	3	1	1	0	1	2	0	0	0	1	0
PLATELET COUNT GRADE 2	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0
PLATELET COUNT GRADE 3	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
LEUKOCYTES GRADE 1	1	1	2	0	0	0	2	1	2	1	0	1	1	3	2	2	1	0	0	0	1	1	0	0	0	1	0
LEUKOCYTES GRADE 2	0	0	0	0	0	1	0	0	1	0	0	1	1	0	0	0	0	0	1	0	0	2	0	1	0	0	0
LEUKOCYTES GRADE 3	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	1	0	0	0	0	0	0	0	0	0	0
LEUKOCYTES GRADE 4	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
ABSOLUTE NEUTROPHIL COUNT DRV. GRADE 1	1	0	0	0	0	1	3	0	2	0	0	1	0	0	0	2	0	0	1	0	0	1	0	1	0	0	0
ABSOLUTE NEUTROPHIL COUNT DRV. GRADE 2	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
ABSOLUTE NEUTROPHIL COUNT DRV. GRADE 3	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	1	0	0	0	0	0
ABSOLUTE NEUTROPHIL COUNT DRV. GRADE 4	0	0	0	0	0	0	1	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: The Number of Participants with Clinical Laboratory Test Abnormalities (LIVER AND KIDNEY FUNCTION)

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End point title

The Number of Participants with Clinical Laboratory Test Abnormalities (LIVER AND KIDNEY FUNCTION) ^[4]

End point description

End point type

Primary

End point timeframe

From baseline to 100 days after last dose (up to approximately 2.5 years)

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 were planned for these endpoints

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	1
Units: Participants
ALKALINE PHOSPHATASE GRADE 1	2	2	2	1	3	5	2	5	6	4	2	3	3	4	0	7	6	2	1	0	3	2	1	0	0	0	1
ALKALINE PHOSPHATASE GRADE 2	1	1	1	2	0	1	1	0	0	0	1	2	0	1	1	3	1	0	1	1	1	2	0	1	0	0	1
ALKALINE PHOSPHATASE GRADE 3	0	0	0	0	0	0	2	2	1	0	0	0	1	0	1	2	0	1	0	0	0	0	0	0	0	1	0
ASPARTATE AMINOTRANSFERASE GRADE 1	2	3	1	1	1	3	4	2	1	2	0	4	2	2	2	10	5	4	3	0	5	2	0	1	1	0	1
ASPARTATE AMINOTRANSFERASE GRADE 2	0	0	1	1	0	0	0	0	1	0	0	1	0	0	2	0	0	1	0	0	0	0	0	0	0	0	1
ASPARTATE AMINOTRANSFERASE GRADE 3	0	0	0	1	0	0	2	1	1	0	2	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
ASPARTATE AMINOTRANSFERASE GRADE 4	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
ALANINE AMINOTRANSFERASE GRADE 1	1	3	2	2	0	2	4	1	2	0	1	4	1	1	2	7	4	3	1	0	3	3	0	1	0	0	1
ALANINE AMINOTRANSFERASE GRADE 2	1	0	0	1	0	0	1	1	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
ALANINE AMINOTRANSFERASE GRADE 3	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
ALANINE AMINOTRANSFERASE GRADE 4	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
BILIRUBIN, TOTAL GRADE 1	0	0	0	0	0	0	1	1	0	0	1	1	0	0	0	2	0	1	0	0	0	0	0	0	0	0	0
BILIRUBIN, TOTAL GRADE 2	0	0	0	2	0	0	1	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	1	1
BILIRUBIN, TOTAL GRADE 3	1	1	1	0	0	0	1	1	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
BILIRUBIN, TOTAL GRADE 4	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
CREATININE GRADE 1	2	1	2	1	0	0	3	6	1	1	0	1	1	3	2	7	0	1	2	1	2	3	1	1	1	1	0
CREATININE GRADE 2	0	1	0	1	1	0	0	0	0	0	0	0	1	0	0	3	2	0	0	0	0	2	0	0	0	0	0
CREATININE GRADE 3	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	2	0	1	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: The Number of Participants with Clinical Laboratory Test Abnormalities (OTHER CHEMISTRY TESTING )

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End point title

The Number of Participants with Clinical Laboratory Test Abnormalities (OTHER CHEMISTRY TESTING ) ^[5]

End point description

End point type

Primary

End point timeframe

From baseline to 100 days after last dose (up to approximately 2.5 years)

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only summary statistics were planned for these endpoints

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	1
Units: Participants
SODIUM, SERUM GRADE 1	4	3	2	2	1	2	6	5	2	2	2	2	2	2	2	4	3	1	0	0	4	1	0	1	0	1	1
SODIUM, SERUM GRADE 2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
SODIUM, SERUM GRADE 3	0	0	1	0	1	0	0	1	0	0	1	0	0	2	0	2	0	2	1	0	0	0	0	0	1	0	1
POTASSIUM, SERUM GRADE 1	0	3	0	2	0	1	4	3	2	2	0	2	3	2	2	8	3	0	1	0	2	2	1	1	0	0	0
POTASSIUM, SERUM GRADE 2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	1	0	1	0	0	0	0	0	0	0	0
POTASSIUM, SERUM GRADE 3	0	0	0	1	1	0	1	0	1	1	0	0	0	1	0	1	0	1	0	0	1	0	0	0	0	0	0
POTASSIUM, SERUM GRADE 4	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
CALCIUM, TOTAL GRADE 1	0	3	1	1	1	3	5	4	2	4	2	4	3	0	2	9	4	1	4	0	1	5	1	0	0	0	0
CALCIUM, TOTAL GRADE 2	1	0	2	0	0	0	1	3	0	0	0	0	0	1	0	1	2	1	0	0	1	0	1	1	0	0	0
CALCIUM, TOTAL GRADE 3	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0
MAGNESIUM, SERUM GRADE 1	1	1	0	2	2	0	1	3	4	1	2	4	0	0	2	6	2	2	0	0	3	1	0	0	0	2	0
MAGNESIUM, SERUM GRADE 2	0	0	0	0	0	1	2	0	0	2	0	0	1	0	0	1	2	0	0	0	0	0	0	0	0	0	0
MAGNESIUM, SERUM GRADE 3	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
GLUCOSE, FASTING SERUM GRADE 1	1	3	0	3	1	4	4	2	2	0	2	6	5	2	2	2	99999	99999	0	99999	0	0	99999	99999	99999	99999	0
GLUCOSE, FASTING SERUM GRADE 2	0	0	1	0	1	0	2	1	0	1	0	1	1	0	0	1	99999	99999	0	99999	1	0	99999	99999	99999	99999	0
GLUCOSE, FASTING SERUM GRADE 3	1	0	1	0	1	1	0	1	0	0	0	0	0	0	0	0	99999	99999	0	99999	0	0	99999	99999	99999	99999	0
ALBUMIN GRADE 1	2	2	1	2	1	2	0	4	1	3	1	2	5	2	1	3	4	2	0	0	1	2	1	0	2	1	0
ALBUMIN GRADE 2	1	2	2	1	1	3	5	3	3	0	2	4	1	2	3	5	2	2	2	1	3	4	0	0	0	1	1
ALBUMIN GRADE 3	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
AMYLASE, TOTAL GRADE 1	1	0	0	0	1	1	0	3	1	0	0	1	0	0	0	2	2	1	1	0	0	1	0	0	0	0	0
AMYLASE, TOTAL GRADE 2	0	1	0	0	0	0	1	0	1	0	1	1	1	1	0	2	0	0	0	0	1	0	0	0	0	0	0
AMYLASE, TOTAL GRADE 3	0	0	2	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
AMYLASE, TOTAL GRADE 4	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0
LIPASE, TOTAL GRADE 1	0	0	0	0	0	0	1	1	1	0	0	1	0	0	1	2	1	1	1	1	1	2	0	0	1	0	0
LIPASE, TOTAL GRADE 2	1	0	0	1	0	0	0	1	1	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0
LIPASE, TOTAL GRADE 3	1	1	0	1	0	0	0	2	0	1	0	1	0	0	0	2	1	2	2	0	1	2	0	0	0	0	0
LIPASE, TOTAL GRADE 4	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	2	1	0	1	0	0	0	0	0	0	1	0

No statistical analyses for this end point

Primary: The number of Participants Experiencing Dose-Limiting Toxicities (DLTs)

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End point title

The number of Participants Experiencing Dose-Limiting Toxicities (DLTs) ^[6]

End point description

The number of participants experiencing dose-limiting toxicities (DLTs) to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. DLTs are defined based on the incidence, severity, and duration of adverse events (AEs) for which no clear alternative cause is identified. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.

End point type

Primary

End point timeframe

From first dose to 28 days after first dose

Notes
[6] - 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 were planned for these endpoints

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	1
Units: Participants	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	1	0	0	0	0	0	1	0	0	0

No statistical analyses for this end point

Primary: The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation

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End point title

The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation ^[7]

End point description

The number of participants experiencing adverse events (AEs) leading to discontinuation of study drug to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.

End point type

Primary

End point timeframe

From first dose to 100 days after last dose (up to approximately 2.5 years)

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only summary statistics were planned for these endpoints

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	1
Units: Participants	0	0	0	0	0	0	0	0	1	0	0	2	0	2	0	0	2	0	2	0	0	1	0	0	0	0	0

No statistical analyses for this end point

Primary: The Number of Participant Deaths

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End point title

The Number of Participant Deaths ^[8]

End point description

The number of deaths in each arm to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors.

End point type

Primary

End point timeframe

From first dose to study completion (up to approximately 5 years)

Notes
[8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only summary statistics were planned for these endpoints

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	1
Units: Participants	4	4	3	4	4	3	7	11	6	6	4	9	7	8	2	16	11	3	3	0	5	4	2	2	1	1	1

No statistical analyses for this end point

Secondary: Objective Response Rate (ORR)

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End point title

Objective Response Rate (ORR)

End point description

The total number of participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR) Baseline is defined as the last non-missing measurement prior to the first dosing date and time.

End point type

Secondary

End point timeframe

From baseline up to approximately 2.5 years

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	9	7	8	5	18	12	6	7	1	6	9	2	2	2	2	0 ^[9]
Units: Participants	0	0	0	0	0	0	2	1	1	1	0	0	0	0	0	1	0	0	1	0	0	2	0	0	0	0

Notes
[9] - BOR was not evaluable for the only patient because of death prior to any tumor assessment.

No statistical analyses for this end point

Secondary: Duration of Response (DOR)

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End point title

Duration of Response (DOR) ^[10]

End point description

The time between the date of first response and the subsequent date of disease progression or death (death after re-treatment will not be considered), whichever occurs first in participants with a best overall response (BOR) of complete response (CR) or partial response (PR). Baseline is defined as the last non-missing measurement prior to the first dosing date and time.

End point type

Secondary

End point timeframe

From baseline up to approximately 2.5 years

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint is specific to Parts 1-8 only

Part 1: BMS 20 mg Q2W

Part 1: BMS 40 mg Q2W

Part 1: BMS 80 mg Q2W

Part 1: BMS 160 mg Q2W

Part 1: BMS 320 mg Q2W

Part 2 BMS 20 mg + Nivo 240 mg Q2W

Part 2: BMS 40 mg + Nivo 240 mg Q2W

Part 2: BMS 80 mg + Nivo 240 mg Q2W

Part 2: BMS 160 mg + Nivo 240 mg Q2W

Part 2: BMS 320 mg + Nivo 240 mg Q2W

Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W

Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W

Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W

Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W

Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W

Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)

Part 4: BMS 80 mg + Nivo 480mg Q4W

Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W

Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W

Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W

Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W

Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W

Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W

Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W

Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W

Part 8: Cohort 4- Nivo 480 mg Q4W

Number of subjects analysed

0 ^[11]

0 ^[12]

0 ^[13]

0 ^[14]

0 ^[15]

0 ^[16]

0 ^[17]

0 ^[18]

0 ^[19]

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]

Units: Weeks

median (confidence interval 95%)

( to )

Notes
[11] - The number of responders within each tumor type was not sufficient for analysis.
[12] - The number of responders within each tumor type was not sufficient for analysis.
[13] - The number of responders within each tumor type was not sufficient for analysis.
[14] - The number of responders within each tumor type was not sufficient for analysis.
[15] - The number of responders within each tumor type was not sufficient for analysis.
[16] - The number of responders within each tumor type was not sufficient for analysis.
[17] - The number of responders within each tumor type was not sufficient for analysis.
[18] - The number of responders within each tumor type was not sufficient for analysis.
[19] - The number of responders within each tumor type was not sufficient for analysis.
[20] - The number of responders within each tumor type was not sufficient for analysis.
[21] - The number of responders within each tumor type was not sufficient for analysis.
[22] - The number of responders within each tumor type was not sufficient for analysis.
[23] - The number of responders within each tumor type was not sufficient for analysis.
[24] - The number of responders within each tumor type was not sufficient for analysis.
[25] - The number of responders within each tumor type was not sufficient for analysis.
[26] - The number of responders within each tumor type was not sufficient for analysis.
[27] - The number of responders within each tumor type was not sufficient for analysis.
[28] - The number of responders within each tumor type was not sufficient for analysis.
[29] - The number of responders within each tumor type was not sufficient for analysis.
[30] - The number of responders within each tumor type was not sufficient for analysis.
[31] - The number of responders within each tumor type was not sufficient for analysis.
[32] - The number of responders within each tumor type was not sufficient for analysis.
[33] - The number of responders within each tumor type was not sufficient for analysis.
[34] - The number of responders within each tumor type was not sufficient for analysis.
[35] - The number of responders within each tumor type was not sufficient for analysis.
[36] - The number of responders within each tumor type was not sufficient for analysis.

No statistical analyses for this end point

Secondary: Progression Free Survival (PFS) Rate at 24 Weeks

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End point title

Progression Free Survival (PFS) Rate at 24 Weeks ^[37]

End point description

The number of treated participants remaining progression free and surviving at 24 weeks since the first dosing date. 99999- Data could not be calculated due to number at risk being less than 5

End point type

Secondary

End point timeframe

24 weeks after first dose

Notes
[37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint is specific to Parts 1-8 only

Part 1: BMS 20 mg Q2W

Part 1: BMS 40 mg Q2W

Part 1: BMS 80 mg Q2W

Part 1: BMS 160 mg Q2W

Part 1: BMS 320 mg Q2W

Part 2 BMS 20 mg + Nivo 240 mg Q2W

Part 2: BMS 40 mg + Nivo 240 mg Q2W

Part 2: BMS 80 mg + Nivo 240 mg Q2W

Part 2: BMS 160 mg + Nivo 240 mg Q2W

Part 2: BMS 320 mg + Nivo 240 mg Q2W

Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W

Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W

Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W

Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W

Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W

Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)

Part 4: BMS 80 mg + Nivo 480mg Q4W

Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W

Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W

Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W

Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W

Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W

Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W

Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W

Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W

Part 8: Cohort 4- Nivo 480 mg Q4W

Number of subjects analysed

Units: Percent of Participants

number (confidence interval 95%)

99999 (99999 to 99999)

No statistical analyses for this end point

Secondary: Cmax: Maximum observed serum concentration

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End point title

Cmax: Maximum observed serum concentration

End point description

The maximum observed serum concentration was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab Note: 99999 = N/A

End point type

Secondary

End point timeframe

Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	0 ^[38]
Units: NG/ML
geometric mean (geometric coefficient of variation)
CYCLE 1 DAY 1	4964 ( 99999 )	11245 ( 99999 )	19254 ( 99999 )	36143 ( 99999 )	68774 ( 99999 )	9424 ( 99999 )	11699 ( 99999 )	19547 ( 99999 )	39182 ( 99999 )	76445 ( 99999 )	7860 ( 99999 )	9345 ( 99999 )	17979 ( 99999 )	55790 ( 99999 )	65472 ( 99999 )	17586 ( 99999 )	19012 ( 99999 )	21399 ( 99999 )	11139 ( 99999 )	99999 ( 99999 )	14267 ( 99999 )	15424 ( 99999 )	3270 ( 99999 )	11300 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 4 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	8960 ( 99999 )	10273 ( 99999 )	20900 ( 99999 )	69922 ( 99999 )	117839 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	31800 ( 99999 )	11261 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	14143 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 5 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	16912 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 9 DAY 1	99999 ( 99999 )	99999 ( 99999 )	23200 ( 99999 )	61500 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	17392 ( 99999 )	23097 ( 99999 )	72991 ( 99999 )	207853 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	30922 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )

Notes
[38] - Only participants with available serum time-concentration data evaluated

No statistical analyses for this end point

Secondary: Tmax: Time of maximum observed serum concentration

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End point title

Tmax: Time of maximum observed serum concentration

End point description

The time of maximum observed serum concentration was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab Note: 99999 = N/A

End point type

Secondary

End point timeframe

Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)

Part 1: BMS 20 mg Q2W

Part 1: BMS 40 mg Q2W

Part 1: BMS 80 mg Q2W

Part 1: BMS 160 mg Q2W

Part 1: BMS 320 mg Q2W

Part 2 BMS 20 mg + Nivo 240 mg Q2W

Part 2: BMS 40 mg + Nivo 240 mg Q2W

Part 2: BMS 80 mg + Nivo 240 mg Q2W

Part 2: BMS 160 mg + Nivo 240 mg Q2W

Part 2: BMS 320 mg + Nivo 240 mg Q2W

Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W

Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W

Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W

Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W

Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W

Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)

Part 4: BMS 80 mg + Nivo 480mg Q4W

Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W

Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W

Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W

Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W

Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W

Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W

Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W

Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W

Part 8: Cohort 4- Nivo 480 mg Q4W

Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine

Number of subjects analysed

0 ^[39]

Units: Hours

median (full range (min-max))

CYCLE 1 DAY 1

0.675 (0.467 to 4.52)

0.575 (0.467 to 0.933)

4.58 (0.500 to 24.0)

2.30 (0.567 to 4.02)

0.558 (0.467 to 4.08)

0.467 (0.467 to 4.00)

2.34 (0.467 to 4.08)

0.517 (0.467 to 4.50)

0.650 (0.517 to 4.10)

0.792 (0.450 to 4.50)

0.667 (0.633 to 4.08)

4.00 (0.467 to 4.13)

4.00 (0.467 to 4.43)

2.55 (0.467 to 24.1)

4.13 (0.467 to 4.62)

4.09 (0.467 to 4.82)

0.550 (0.500 to 24.0)

2.30 (0.467 to 4.55)

0.583 (0.467 to 4.08)

99999 (99999 to 99999)

4.00 (0.517 to 23.0)

0.475 (0.467 to 4.75)

0.533 (0.533 to 0.533)

4.83 (4.83 to 4.83)

99999 (99999 to 99999)

( to )

CYCLE 4 DAY 1

99999 (99999 to 99999)

0.583 (0.583 to 0.583)

4.00 (0.617 to 24.0)

0.583 (0.583 to 0.583)

4.00 (0.467 to 24.9)

2.58 (0.467 to 4.68)

99999 (99999 to 99999)

4.03 (4.03 to 4.03)

0.517 (0.500 to 0.583)

99999 (99999 to 99999)

0.467 (0.000 to 4.00)

99999 (99999 to 99999)

( to )

CYCLE 5 DAY 1

99999 (99999 to 99999)

0.550 (0.517 to 0.583)

99999 (99999 to 99999)

( to )

CYCLE 9 DAY 1

99999 (99999 to 99999)

0.467 (0.467 to 0.467)

22.7 (22.7 to 22.7)

99999 (99999 to 99999)

0.567 (0.467 to 4.00)

4.47 (4.02 to 4.50)

2.38 (0.633 to 4.12)

4.05 (3.98 to 23.9)

99999 (99999 to 99999)

3.94 (0.500 to 4.03)

99999 (99999 to 99999)

( to )

Notes
[39] - Only participants with available serum time-concentration data evaluated

No statistical analyses for this end point

Secondary: AUC(0-t): Area under the serum concentration-time curve from time 0 to time t

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End point title

AUC(0-t): Area under the serum concentration-time curve from time 0 to time t

End point description

The area under the serum concentration-time curve from time 0 to time t was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab Note: 99999 = N/A

End point type

Secondary

End point timeframe

Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	0 ^[40]
Units: H*NG/ML
geometric mean (geometric coefficient of variation)
CYCLE 1 DAY 1	577541 ( 99999 )	1678196 ( 99999 )	1825502 ( 99999 )	5024906 ( 99999 )	9981469 ( 99999 )	609426 ( 99999 )	1495494 ( 99999 )	2324225 ( 99999 )	5458640 ( 99999 )	8694104 ( 99999 )	1047354 ( 99999 )	1197507 ( 99999 )	2774058 ( 99999 )	7257441 ( 99999 )	10580541 ( 99999 )	2351794 ( 99999 )	2000522 ( 99999 )	3216650 ( 99999 )	1251698 ( 99999 )	99999 ( 99999 )	1653102 ( 99999 )	864500 ( 99999 )	390424 ( 99999 )	2399055 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 4 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	773957 ( 99999 )	2210404 ( 99999 )	2400433 ( 99999 )	10729551 ( 99999 )	23851864 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	2699238 ( 99999 )	1837861 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	504998 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 5 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	2520673 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 9 DAY 1	99999 ( 99999 )	99999 ( 99999 )	3952990 ( 99999 )	13024914 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	2971409 ( 99999 )	1247687 ( 99999 )	16483279 ( 99999 )	28499982 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	4537054 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )

Notes
[40] - Only participants with available serum time-concentration data evaluated

No statistical analyses for this end point

Secondary: AUC(TAU): Area under the serum concentration-time curve in 1 dosing interval

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End point title

AUC(TAU): Area under the serum concentration-time curve in 1 dosing interval

End point description

The area under the serum concentration-time curve in 1 dosing interval was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab Note: 99999 = N/A

End point type

Secondary

End point timeframe

Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	0 ^[41]
Units: H*NG/ML
geometric mean (geometric coefficient of variation)
CYCLE 1 DAY 1	577541 ( 99999 )	1599886 ( 99999 )	3142196 ( 99999 )	5854143 ( 99999 )	9981469 ( 99999 )	663257 ( 99999 )	1515139 ( 99999 )	2551115 ( 99999 )	5458640 ( 99999 )	11483961 ( 99999 )	1383126 ( 99999 )	1521223 ( 99999 )	3133192 ( 99999 )	7464248 ( 99999 )	11966698 ( 99999 )	2602049 ( 99999 )	2734577 ( 99999 )	3500606 ( 99999 )	1568004 ( 99999 )	99999 ( 99999 )	1705864 ( 99999 )	1410042 ( 99999 )	447709 ( 99999 )	2812249 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 4 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	2210404 ( 99999 )	99999 ( 99999 )	12666237 ( 99999 )	27936423 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1837861 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	3590883 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 5 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	3335668 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 9 DAY 1	99999 ( 99999 )	99999 ( 99999 )	3952990 ( 99999 )	13024914 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	3345948 ( 99999 )	3307867 ( 99999 )	16483279 ( 99999 )	50254284 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	6176469 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )

Notes
[41] - Only participants with available serum time-concentration data evaluated

No statistical analyses for this end point

Secondary: Ctau: Observed serum concentration at the end of a dosing interval when intensive samples are collected

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End point title

Ctau: Observed serum concentration at the end of a dosing interval when intensive samples are collected

End point description

The observed serum concentration at the end of a dosing interval when intensive samples are collected was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab Note: 99999 = N/A

End point type

Secondary

End point timeframe

Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	0 ^[42]
Units: NG/ML
geometric mean (geometric coefficient of variation)
CYCLE 1 DAY 1	657 ( 99999 )	2577 ( 99999 )	5354 ( 99999 )	10852 ( 99999 )	16514 ( 99999 )	756 ( 99999 )	1904 ( 99999 )	3598 ( 99999 )	10413 ( 99999 )	18596 ( 99999 )	885 ( 99999 )	604 ( 99999 )	2335 ( 99999 )	3059 ( 99999 )	7739 ( 99999 )	3928 ( 99999 )	544 ( 99999 )	1725 ( 99999 )	790 ( 99999 )	99999 ( 99999 )	1535 ( 99999 )	1533 ( 99999 )	0.004 ( 99999 )	42.9 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 4 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	2527 ( 99999 )	99999 ( 99999 )	7729 ( 99999 )	32982 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1262 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	6906 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 5 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1412 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 9 DAY 1	99999 ( 99999 )	99999 ( 99999 )	6470 ( 99999 )	33600 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	5510 ( 99999 )	5686 ( 99999 )	34303 ( 99999 )	131520 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	13400 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )

Notes
[42] - Only participants with available serum time-concentration data evaluated

No statistical analyses for this end point

Secondary: CLT: Total body clearance

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End point title

CLT: Total body clearance

End point description

The total body clearance was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab Note: 99999 = N/A

End point type

Secondary

End point timeframe

Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	0 ^[43]
Units: L/H
geometric mean (geometric coefficient of variation)
CYCLE 4 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	0.018 ( 99999 )	99999 ( 99999 )	0.013 ( 99999 )	0.011 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	0.022 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	0.011 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 5 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	0.024 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 9 DAY 1	99999 ( 99999 )	99999 ( 99999 )	0.020 ( 99999 )	0.012 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	0.012 ( 99999 )	0.024 ( 99999 )	0.010 ( 99999 )	0.006 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	0.013 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )

Notes
[43] - Only participants with available serum time-concentration data evaluated

No statistical analyses for this end point

Secondary: Css-avg: Average concentration over a dosing interval (AUC(TAU)/tau)

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End point title

Css-avg: Average concentration over a dosing interval (AUC(TAU)/tau)

End point description

The average concentration over a dosing interval (AUC(TAU)/tau) was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab Note: 99999 = N/A

End point type

Secondary

End point timeframe

Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	0 ^[44]
Units: NG/ML
geometric mean (geometric coefficient of variation)
CYCLE 4 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	4379 ( 99999 )	99999 ( 99999 )	25131 ( 99999 )	55386 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	3715 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	10739 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 5 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	4964 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 9 DAY 1	99999 ( 99999 )	99999 ( 99999 )	11826 ( 99999 )	45155 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	9746 ( 99999 )	9903 ( 99999 )	45878 ( 99999 )	148579 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	19538 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )

Notes
[44] - Only participants with available serum time-concentration data evaluated

No statistical analyses for this end point

Secondary: AI: Accumulation Index. Ratio of an exposure measure at steady state (Cmax)

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End point title

AI: Accumulation Index. Ratio of an exposure measure at steady state (Cmax)

End point description

The ratio of an exposure measure at steady state to that after the first dose was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab Note: 99999 = N/A

End point type

Secondary

End point timeframe

Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	0 ^[45]
Units: NG/ML
geometric mean (geometric coefficient of variation)
CYCLE 4 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	0.793 ( 99999 )	1.05 ( 99999 )	1.67 ( 99999 )	1.40 ( 99999 )	1.52 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1.32 ( 99999 )	1.03 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1.21 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 5 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1.02 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 9 DAY 1	99999 ( 99999 )	99999 ( 99999 )	1.45 ( 99999 )	1.89 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1.40 ( 99999 )	1.29 ( 99999 )	1.83 ( 99999 )	2.56 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1.66 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )

Notes
[45] - Only participants with available serum time-concentration data evaluated

No statistical analyses for this end point

Secondary: AI: Accumulation Index. Ratio of an exposure measure at steady state (AUC)

Top of page

End point title

AI: Accumulation Index. Ratio of an exposure measure at steady state (AUC)

End point description

End point type

Secondary

End point timeframe

Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	0 ^[46]
Units: H*NG/ML
geometric mean (geometric coefficient of variation)
CYCLE 4 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1.28 ( 99999 )	99999 ( 99999 )	1.56 ( 99999 )	1.77 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	0.000 ( 99999 )	1.37 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	2.13 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 5 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1.21 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 9 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	2.21 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1.85 ( 99999 )	0.748 ( 99999 )	2.78 ( 99999 )	4.40 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	2.32 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )

Notes
[46] - Only participants with available serum time-concentration data evaluated

No statistical analyses for this end point

Secondary: AI: Accumulation Index. Ratio of an exposure measure at steady state (Ctau)

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End point title

AI: Accumulation Index. Ratio of an exposure measure at steady state (Ctau)

End point description

End point type

Secondary

End point timeframe

Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	0 ^[47]
Units: NG/ML
geometric mean (geometric coefficient of variation)
CYCLE 4 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1.90 ( 99999 )	99999 ( 99999 )	1.22 ( 99999 )	1.89 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	0.000 ( 99999 )	2.47 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	2.72 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 5 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1.05 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 9 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	2.33 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	2.40 ( 99999 )	1.22 ( 99999 )	2.61 ( 99999 )	7.55 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	3.49 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )

Notes
[47] - Only participants with available serum time-concentration data evaluated

No statistical analyses for this end point

Secondary: T-HALFeff: Effective elimination half-life that explains the degree of accumulation observed for a specific exposure measure (exposure measure includes AUC(TAU), Cmax)

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End point title

T-HALFeff: Effective elimination half-life that explains the degree of accumulation observed for a specific exposure measure (exposure measure includes AUC(TAU), Cmax)

End point description

The effective elimination half-life that explains the degree of accumulation observed for a specific exposure measure was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab Note: 99999 = N/A

End point type

Secondary

End point timeframe

Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	0 ^[48]
Units: Hr
arithmetic mean (standard deviation)
CYCLE 4 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	229 ( 40 )	99999 ( 99999 )	345 ( 111 )	429 ( 182 )	99999 ( 99999 )	99999 ( 99999 )	0.000 ( 99999 )	261 ( 58 )	99999 ( 99999 )	99999 ( 99999 )	146 ( 200 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 5 DAY 1	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	447 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 9 DAY 1	99999 ( 99999 )	99999 ( 99999 )	0.000 ( 99999 )	331 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	315 ( 119 )	0.000 ( 0.000 )	593 ( 308 )	607 ( 527 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	312 ( 180 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )

Notes
[48] - Only participants with available serum time-concentration data evaluated

No statistical analyses for this end point

Secondary: Ctrough: Trough observed plasma concentration

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End point title

Ctrough: Trough observed plasma concentration

End point description

Trough observed plasma concentration (this includes predose concentrations and Ctau concentrations) was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab Note: 99999 = N/A

End point type

Secondary

End point timeframe

Cycle 1-17 timepoints can include (Pre-dose, 336, 504, 672 hours post dose)

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	4	4	4	4	4	7	8	12	8	8	4	10	7	8	6	18	12	6	7	1	6	9	2	2	2	2	0 ^[49]
Units: ng/mL
geometric mean (geometric coefficient of variation)
CYCLE 1 DAY 29 0 h	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1354 ( 99999 )	1108 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 1 DAY 15 336 h	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1535 ( 99999 )	1912 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 2 DAY 1 0 h	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1391 ( 99999 )	1107 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 2 DAY 1 336 h	657 ( 99999 )	2372 ( 99999 )	5354 ( 99999 )	10852 ( 99999 )	16514 ( 99999 )	561 ( 99999 )	1995 ( 99999 )	4006 ( 99999 )	10413 ( 99999 )	18596 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	4070 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 2 DAY 1 504 h	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	456 ( 99999 )	591 ( 99999 )	2401 ( 99999 )	1921 ( 99999 )	7739 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	2166 ( 99999 )	745 ( 99999 )	1030 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 2 DAY 1 672 h	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	676 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 3 DAY 1 0 h	1290 ( 99999 )	4244 ( 99999 )	5903 ( 99999 )	16974 ( 99999 )	21571 ( 99999 )	614 ( 99999 )	1825 ( 99999 )	4498 ( 99999 )	16379 ( 99999 )	28282 ( 99999 )	323 ( 99999 )	2049 ( 99999 )	4894 ( 99999 )	2766 ( 99999 )	20410 ( 99999 )	5055 ( 99999 )	1480 ( 99999 )	62.5 ( 99999 )	689 ( 2006 )	99999 ( 99999 )	99999 ( 99999 )	2469 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 4 DAY 1 0 h	3420 ( 99999 )	4593 ( 99999 )	7169 ( 99999 )	20703 ( 99999 )	26090 ( 99999 )	358 ( 99999 )	2095 ( 99999 )	5108 ( 99999 )	20800 ( 99999 )	47108 ( 99999 )	1080 ( 99999 )	1971 ( 99999 )	5140 ( 99999 )	12649 ( 99999 )	32150 ( 99999 )	7252 ( 99999 )	1466 ( 99999 )	99999 ( 99999 )	754 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	5461 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 4 DAY 29 0	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1856 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 4 DAY 15 336 h	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	2130 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 5 DAY 1 0 h	99999 ( 99999 )	6600 ( 99999 )	13491 ( 99999 )	13300 ( 99999 )	35200 ( 99999 )	386 ( 99999 )	1301 ( 99999 )	7468 ( 99999 )	26813 ( 99999 )	90700 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	9811 ( 99999 )	1671 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 5 DAY 1 504 h	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	2527 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	18771 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	1262 ( 129 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 6 DAY 1 0 h	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	604 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 6 DAY 1 672 h	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	62.5 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 7 DAY 1 0 h	99999 ( 99999 )	5390 ( 99999 )	10217 ( 99999 )	22073 ( 99999 )	99999 ( 99999 )	946 ( 99999 )	4777 ( 99999 )	12527 ( 99999 )	32753 ( 99999 )	76970 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	11471 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 9 DAY 1 0 h	99999 ( 99999 )	99999 ( 99999 )	6300 ( 99999 )	31300 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	6397 ( 99999 )	13536 ( 99999 )	29902 ( 99999 )	106710 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	12905 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	579 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 10 DAY 1 0 h	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	29100 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 10 DAY 1 336 h	99999 ( 99999 )	99999 ( 99999 )	6470 ( 99999 )	33600 ( 99999 )	99999 ( 99999 )	1190 ( 99999 )	8264 ( 99999 )	5686 ( 99999 )	28988 ( 99999 )	131520 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	13400 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )
CYCLE 17 DAY 1 0 h	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	48500 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	16600 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	( )

Notes
[49] - Only participants with available serum time-concentration data evaluated

No statistical analyses for this end point

Secondary: Frequency of Positive Anti-Drug Antibodies (ADA) to BMS-986178

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End point title

Frequency of Positive Anti-Drug Antibodies (ADA) to BMS-986178 ^[50]

End point description

The number of participants with positive anti-drug antibodies (ADA) is assessed to characterize the immunogenicity of BMS-986178 administered alone or in combination with nivolumab and/or ipilimumab. ADA Positive: A participant with at least one ADA-positive sample relative to baseline (ADA negative at baseline or ADA titer to be at least 4-fold or greater (>=) than baseline positive titer) at any time after initiation of treatment.

End point type

Secondary

End point timeframe

Cycle 1-6 timepoints can include (Pre-dose, 696 hours post dose)

Notes
[50] - 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: Endpoint is specific to Participants treated with BMS-986178

End point values	Part 1: BMS 20 mg Q2W	Part 1: BMS 40 mg Q2W	Part 1: BMS 80 mg Q2W	Part 1: BMS 160 mg Q2W	Part 1: BMS 320 mg Q2W	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	1	2	3	3	3	6	6	6	7	5	2	5	6	7	6	0 ^[51]	2	0 ^[52]	0 ^[53]	0 ^[54]	0 ^[55]	3	1	1	0 ^[56]	0 ^[57]
Units: Positive anti-drug antibodies (ADA)	0	0	1	0	0	3	1	3	1	0	1	3	1	4	2		1					0	0	0

Notes
[51] - Participants with Baseline and at Least One Post-baseline ADA Assessment analyzed only
[52] - Participants with Baseline and at Least One Post-baseline ADA Assessment analyzed only
[53] - Participants with Baseline and at Least One Post-baseline ADA Assessment analyzed only
[54] - Participants with Baseline and at Least One Post-baseline ADA Assessment analyzed only
[55] - Participants with Baseline and at Least One Post-baseline ADA Assessment analyzed only
[56] - Participants with Baseline and at Least One Post-baseline ADA Assessment analyzed only
[57] - Participants with Baseline and at Least One Post-baseline ADA Assessment analyzed only

No statistical analyses for this end point

Secondary: Frequency of Positive Anti-Drug Antibodies (ADA) to Nivolumab

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End point title

Frequency of Positive Anti-Drug Antibodies (ADA) to Nivolumab ^[58]

End point description

The number of participants with positive anti-drug antibodies (ADA) is assessed to characterize the immunogenicity of Nivolumab administered with BMS-986178 ADA Positive: A participant with at least one ADA-positive sample relative to baseline (ADA negative at baseline or ADA titer to be at least 4-fold or greater (>=) than baseline positive titer) at any time after initiation of treatment.

End point type

Secondary

End point timeframe

Cycle 1-6 timepoints can include (Pre-dose, 696 hours post dose)

Notes
[58] - 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: Endpoint is specific to Participants treated with Nivolumab

End point values	Part 2 BMS 20 mg + Nivo 240 mg Q2W	Part 2: BMS 40 mg + Nivo 240 mg Q2W	Part 2: BMS 80 mg + Nivo 240 mg Q2W	Part 2: BMS 160 mg + Nivo 240 mg Q2W	Part 2: BMS 320 mg + Nivo 240 mg Q2W	Part 2C: BMS 80 mg + Nivo 240 mg Q2W (BDC)	Part 4: BMS 80 mg + Nivo 480mg Q4W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	5	7	8	8	6	17	9	5	1	5	9	0 ^[59]	1	0 ^[60]	1	0 ^[61]
Units: Positive anti-drug antibodies (ADA)	0	1	1	0	0	3	0	0	0	1	1		1		0

Notes
[59] - Participants with Baseline and at Least One Post-baseline ADA Assessment analyzed only
[60] - Participants with Baseline and at Least One Post-baseline ADA Assessment analyzed only
[61] - Participants with Baseline and at Least One Post-baseline ADA Assessment analyzed only

No statistical analyses for this end point

Secondary: Frequency of Positive Anti-Drug Antibodies (ADA) to Ipilimumab.

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End point title

Frequency of Positive Anti-Drug Antibodies (ADA) to Ipilimumab. ^[62]

End point description

The number of participants with anti-drug antibodies (ADA) is assessed to characterize the immunogenicity of Ipilimumab administered with BMS-986178 ADA Positive: A participant with at least one ADA-positive sample relative to baseline (ADA negative at baseline or ADA titer to be at least 4-fold or greater (>=) than baseline positive titer) at any time after initiation of treatment.

End point type

Secondary

End point timeframe

Cycle 1-6 timepoints can include (Pre-dose, 696 hours post dose)

Notes
[62] - 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: Endpoint is specific to Participants treated with Ipilimumab

End point values	Part 3: BMS 20 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 40 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 80 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 160 mg + Ipi 1 mg/kg Q3W	Part 3: BMS 320 mg + Ipi 1 mg/kg Q3W	Part 5: BMS 80 mg + Ipi 3 mg/kg Q3W	Part 6A:BMS40mg+Nivo 240mg+Ipi 1mg/kgQ3W/BMS 40mg+Nivo480mgQ4W	Part6B:BMS40mg+Nivo240 mg+Ipi1mg/kgQ3W/BMS 40 mg+Nivo480 mgQ4W	Part 7A: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W	Part 7B: BMS 40mg Q2W + Nivo 240 mg Q2W + Ipi 1 mg/kg Q6W
Number of subjects analysed	4	5	7	7	6	6	6	1	5	9
Units: Positive anti-drug antibodies (ADA)	0	0	1	0	1	0	0	0	0	0

No statistical analyses for this end point

Secondary: The Number of Participants Showing a Change in Soluble OX40 and Peripheral OX40 Receptor Occupancy Pharmacodynamic Biomarkers in Part 8

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End point title

The Number of Participants Showing a Change in Soluble OX40 and Peripheral OX40 Receptor Occupancy Pharmacodynamic Biomarkers in Part 8 ^[63]

End point description

The Number of Participants Showing a Change in Soluble OX40 and Peripheral OX40 Receptor Occupancy Pharmacodynamic Biomarkers in Part 8. A threshold of 80% receptor occupancy following treatment was applied. Note: 99999 = N/A

End point type

Secondary

End point timeframe

Cycle 1-6 timepoints can include (Pre-dose, 24, 168, 336, 672, 1848 hours post dose)

Notes
[63] - 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: Endpoint is specific to Part 8 only

End point values	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W
Number of subjects analysed	1	2	1	1
Units: Participants
Soluble OX40	99999	99999	99999	99999
Peripheral OX40 receptor occupancy (CD4+ T cells)	1	2	1	0
Peripheral OX40 receptor occupancy (Tregs)	1	1	1	0

No statistical analyses for this end point

Secondary: Tumor Pharmacodynamics of BMS-986178 in Combination with Nivolumab or Nivolumab Monotherapy in Part 8

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End point title

Tumor Pharmacodynamics of BMS-986178 in Combination with Nivolumab or Nivolumab Monotherapy in Part 8 ^[64]

End point description

Tumor pharmacodynamics of BMS-986178 in combination with nivolumab or nivolumab monotherapy

End point type

Secondary

End point timeframe

Screening, cycle 1-2 timepoints can include (Pre-dose, 336, 1848 hours post dose)

Notes
[64] - 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: Endpoint is specific to Part 8 only

End point values	Part 8: Cohort 1- BMS 20 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 2- BMS 40 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 3- BMS 80 mg Q12W + Nivo 480 mg Q4W	Part 8: Cohort 4- Nivo 480 mg Q4W
Number of subjects analysed	0 ^[65]	0 ^[66]	0 ^[67]	0 ^[68]
Units: N/A
number (not applicable)

Notes
[65] - Tumor pharmacodynamic readouts not possible due to only 1 matched pair
[66] - Tumor pharmacodynamic readouts not possible due to only 1 matched pair
[67] - Tumor pharmacodynamic readouts not possible due to only 1 matched pair
[68] - Tumor pharmacodynamic readouts not possible due to only 1 matched pair

No statistical analyses for this end point

Secondary: The number of Participants with Sustained T Cell Expansion with DPV-001 in Combination with Nivolumab or Nivolumab Monotherapy in Part 9

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End point title

The number of Participants with Sustained T Cell Expansion with DPV-001 in Combination with Nivolumab or Nivolumab Monotherapy in Part 9 ^[69]

End point description

The number of participants with Sustained T Cell Expansion with DPV-001 in Combination with Nivolumab or Nivolumab Monotherapy was assessed to show a change in pharmacodynamics biomarkers

End point type

Secondary

End point timeframe

Cycle 1-6 timepoints can include (Pre-dose, 24, 168, 336, 672, 1848 hours post dose)

Notes
[69] - 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: Endpoint is specific to Part 9 only

End point values	Part 9: BMS 40 mg Q4W + Nivo 480 mg Q4W + DRibble Vaccine
Number of subjects analysed	0 ^[70]
Units: Participants
number (not applicable)

Notes
[70] - Only participants with available pharmacodynamic data evaluated

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

AEs collected were reported between the first dose and 100 days after the last dose of study medication and on or prior to the first dose of re-treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.1

Reporting group title

BMS-986178 ESC 20 MG

Reporting group description

Subjects with Advanced solid tumors were administered 20 mg BMS-986178 intravenously (IV) over 30 minutes Q2W upto 24 weeks.

Reporting group title

BMS-986178 ESC 40 MG

Reporting group description

Subjects with Advanced solid tumors were administered 40 mg BMS-986178 IV over 30 minutes Q2W upto 24 weeks.

Reporting group title

BMS-986178 ESC 80 MG

Reporting group description

Subjects with Advanced solid tumors were administered 80 mg BMS-986178 IV over 30 minutes Q2W upto 24 weeks.

Reporting group title

BMS-986178 ESC 160 MG

Reporting group description

Subjects with Advanced solid tumors were administered 160 mg BMS-986178 IV over 30 minutes Q2W upto 24 weeks.

Reporting group title

BMS-986178 ESC 320 MG

Reporting group description

Subjects with Advanced solid tumors were administered 320 mg BMS-986178 IV over 30 minutes Q2W upto 24 weeks.

Reporting group title

BMS-986178 ESC 20 MG+NIVO 240 MG

Reporting group description

Subjects with Advanced solid tumors were administered 20 mg BMS-986178 and 240 mg Nivolumab IV over 30 minutes each separately Q2W upto 24 weeks.

Reporting group title

BMS-986178 ESC 80 MG+NIVO 240 MG

Reporting group description

Subjects with Advanced solid tumors were administered 80 mg BMS-986178 and 240 mg Nivolumab IV over 30 minutes each separately Q2W upto 24 weeks.

Reporting group title

BMS-986178 ESC 40 MG+NIVO 240 MG

Reporting group description

Subjects with Advanced solid tumors were administered 40 mg BMS-986178 and 240 mg Nivolumab IV over 30 minutes each separately Q2W upto 24 weeks.

Reporting group title

BMS-986178 ESC 160 MG+NIVO 240 MG

Reporting group description

Subjects with Advanced solid tumors were administered 160 mg BMS-986178 and 240 mg Nivolumab IV over 30 minutes each separately Q2W upto 24 weeks.

Reporting group title

BMS-986178 EXP 80 MG+NIVO 240 MG (BLADDER CANCER)

Reporting group description

Subjects with Bladder cancer were administered 80 mg BMS-986178 and 240 mg Nivolumab IV over 30 minutes each separately Q2W upto 24 weeks.

Reporting group title

BMS-986178 ESC 320 MG+NIVO 240 MG

Reporting group description

Subjects with Advanced solid tumors were administered 320 mg BMS-986178 and 240 mg Nivolumab IV over 30 minutes each separately Q2W upto 24 weeks.

Reporting group title

BMS-986178 ESC 40 MG+IPI 1 MG/KG

Reporting group description

Subjects with Advanced solid tumors were administered 40 mg BMS-986178 and 1 mg/kg Ipilimumab IV over 30 minutes each separately Q3W upto 24 weeks.

Reporting group title

BMS-986178 ESC 20 MG+IPI 1 MG/KG

Reporting group description

Subjects with Advanced solid tumors were administered 20 mg BMS-986178 and 1 mg/kg Ipilimumab IV over 30 minutes each separately Q3W upto 24 weeks.

Reporting group title

BMS-986178 ESC 80 MG+IPI 1 MG/KG

Reporting group description

Subjects with Advanced solid tumors were administered 80 mg BMS-986178 and 1 mg/kg Ipilimumab IV over 30 minutes each separately Q3W upto 24 weeks.

Reporting group title

BMS-986178 ESC 160 MG+IPI 1 MG/KG

Reporting group description

Subjects with Advanced solid tumors were administered 160 mg BMS-986178 and 1 mg/kg Ipilimumab IV over 30 minutes each separately Q3W upto 24 weeks.

Reporting group title

BMS-986178 EPL 80 MG+NIVO 480 MG

Reporting group description

Subjects with Advanced solid tumors were administered 80 mg BMS-986178 and 480 mg Nivolumab IV over 30 minutes each separately Q4W upto 24 weeks.

Reporting group title

BMS-986178 ESC 320 MG+IPI 1 MG/KG

Reporting group description

Subjects with Advanced solid tumors were administered 320 mg BMS-986178 and 1 mg/kg Ipilimumab IV over 30 minutes each separately Q3W upto 24 weeks.

Reporting group title

BMS-986178 EPL 80 MG+IPI 3 MG/KG

Reporting group description

Subjects with Advanced solid tumors 80 mg BMS-986178 and 3 mg/kg Ipilimumab IV over 30 minutes each separately Q3W upto 24 weeks.

Reporting group title

BMS-986178 EXP 40 MG+NIVO 240/480 MG+IPI 1 MG/KG (RCC)

Reporting group description

Subjects with RCC were administered 40 mg BMS-986178 and 240 mg Nivolumab and 1 mg/kg Ipilimumab Q3W IV over 30 minutes each separately followed by 40 mg BMS-986178 and 480 mg Nivolumab IV over 30 minutes each separately Q4W upto 24 weeks.

Reporting group title

BMS-986178 SAF 40 MG+NIVO 240/480 MG+IPI 1 MG/KG (RCC)

Reporting group description

Subjects with Renal cell carcinoma (RCC) were administered 40 mg BMS-986178 and 240 mg Nivolumab and 1 mg/kg Ipilimumab Q3W IV over 30 minutes each separately followed by 40 mg BMS-986178 and 480 mg Nivolumab IV over 30 minutes each separately Q4W upto 24 weeks.

Reporting group title

BMS-986178 SAF 40 MG+NIVO 240 MG+IPI 1 MG/KG (NSCLC)

Reporting group description

Subjects with Non-small cell lung cancer (NSCLC) were administered 40 mg BMS-986178 Q2W and 240 mg Nivolumab each separately Q2W and 1 mg/kg Ipilimumab Q6W upto 24 weeks.

Reporting group title

BMS-986178 EPL 20 MG+NIVO 480 MG (BLADDER CANCER)

Reporting group description

Subjects with Bladder cancer were administered 20 mg BMS-986178 Q12W and 480 mg Nivolumab IV over 30 minutes each separately Q4W upto 24 months or until protocol specified discontinuation criteria.

Reporting group title

NIVO 480 MG EPL (BLADDER CANCER)

Reporting group description

Subjects with Bladder cancer were administered 480 mg Nivolumab IV and Tetanus vaccine intramuscularly on Cycle 1 Day 1 each separately upto 24 months or until protocol specified discontinuation criteria.

Reporting group title

BMS-986178 EPL 40 MG+NIVO 480 MG (BLADDER CANCER)

Reporting group description

Subjects with Bladder cancer were administered 40 mg BMS-986178 Q12W and 480 mg Nivolumab IV over 30 minutes each separately Q4W upto 24 months or until protocol specified discontinuation criteria.

Reporting group title

BMS-986178 EXP 40 MG+NIVO 240 MG+IPI 1 MG/KG (NSCLC)

Reporting group description

Subjects with NSCLC were administered 40 mg BMS-986178 Q2W and 240 mg Nivolumab each separately Q2W and 1 mg/kg Ipilimumab Q6W upto 24 weeks.

Reporting group title

BMS-986178 EPL 80 MG+NIVO 480 MG (BLADDER CANCER)

Reporting group description

Subjects with Bladder cancer were administered 80 mg BMS-986178 Q12W and 480 mg Nivolumab IV over 30 minutes each separately Q4W upto 24 months or until protocol specified discontinuation criteria.

Reporting group title

BMS-986178 EXP 40 MG+NIVO 480 MG+DPV 1

Reporting group description

Subjects with Triple negative Breast cancer were administered 40 mg BMS-986178 Q4W, 480 mg Nivolumab Q4W IV over 30 minutes each separately and 1 mg DPV-001 until end of the treatment.

BMS-986178 ESC 20 MG

BMS-986178 ESC 40 MG

BMS-986178 ESC 80 MG

BMS-986178 ESC 160 MG

BMS-986178 ESC 320 MG

BMS-986178 ESC 20 MG+NIVO 240 MG

BMS-986178 ESC 80 MG+NIVO 240 MG

BMS-986178 ESC 40 MG+NIVO 240 MG

BMS-986178 ESC 160 MG+NIVO 240 MG

BMS-986178 EXP 80 MG+NIVO 240 MG (BLADDER CANCER)

BMS-986178 ESC 320 MG+NIVO 240 MG

BMS-986178 ESC 40 MG+IPI 1 MG/KG

BMS-986178 ESC 20 MG+IPI 1 MG/KG

BMS-986178 ESC 80 MG+IPI 1 MG/KG

BMS-986178 ESC 160 MG+IPI 1 MG/KG

BMS-986178 EPL 80 MG+NIVO 480 MG

BMS-986178 ESC 320 MG+IPI 1 MG/KG

BMS-986178 EPL 80 MG+IPI 3 MG/KG

BMS-986178 EXP 40 MG+NIVO 240/480 MG+IPI 1 MG/KG (RCC)

BMS-986178 SAF 40 MG+NIVO 240/480 MG+IPI 1 MG/KG (RCC)

BMS-986178 SAF 40 MG+NIVO 240 MG+IPI 1 MG/KG (NSCLC)

BMS-986178 EPL 20 MG+NIVO 480 MG (BLADDER CANCER)

NIVO 480 MG EPL (BLADDER CANCER)

BMS-986178 EPL 40 MG+NIVO 480 MG (BLADDER CANCER)

BMS-986178 EXP 40 MG+NIVO 240 MG+IPI 1 MG/KG (NSCLC)

BMS-986178 EPL 80 MG+NIVO 480 MG (BLADDER CANCER)

BMS-986178 EXP 40 MG+NIVO 480 MG+DPV 1

Total subjects affected by serious adverse events

subjects affected / exposed

3 / 4 (75.00%)

4 / 4 (100.00%)

2 / 4 (50.00%)

3 / 4 (75.00%)

3 / 7 (42.86%)

7 / 12 (58.33%)

6 / 8 (75.00%)

4 / 8 (50.00%)

11 / 18 (61.11%)

5 / 8 (62.50%)

6 / 10 (60.00%)

2 / 4 (50.00%)

6 / 7 (85.71%)

5 / 8 (62.50%)

7 / 12 (58.33%)

2 / 6 (33.33%)

4 / 6 (66.67%)

1 / 1 (100.00%)

4 / 7 (57.14%)

6 / 6 (100.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

5 / 9 (55.56%)

1 / 2 (50.00%)

1 / 1 (100.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Malignant ascites

subjects affected / exposed

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malignant neoplasm progression

subjects affected / exposed

3 / 4 (75.00%)

2 / 4 (50.00%)

1 / 4 (25.00%)

1 / 7 (14.29%)

5 / 12 (41.67%)

3 / 8 (37.50%)

1 / 8 (12.50%)

6 / 18 (33.33%)

4 / 8 (50.00%)

5 / 10 (50.00%)

2 / 4 (50.00%)

5 / 7 (71.43%)

4 / 8 (50.00%)

1 / 12 (8.33%)

1 / 6 (16.67%)

0 / 1 (0.00%)

2 / 7 (28.57%)

4 / 6 (66.67%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 2 (0.00%)

1 / 9 (11.11%)

0 / 2 (0.00%)

1 / 1 (100.00%)

occurrences causally related to treatment / all

0 / 3

0 / 2

0 / 1

0 / 5

0 / 4

0 / 1

0 / 6

0 / 5

0 / 2

0 / 5

0 / 1

0 / 0

0 / 3

0 / 5

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 3

0 / 2

0 / 1

0 / 2

0 / 1

0 / 0

0 / 5

0 / 4

0 / 1

0 / 6

0 / 4

0 / 2

0 / 5

0 / 4

0 / 1

0 / 0

0 / 1

0 / 4

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

Metastases to spine

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

1 / 8 (12.50%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pericarditis malignant

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Haemorrhage

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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

Fatigue

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pain

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

1 / 8 (12.50%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyrexia

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

2 / 18 (11.11%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 6 (16.67%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Dyspnoea

subjects affected / exposed

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

1 / 7 (14.29%)

0 / 8 (0.00%)

2 / 12 (16.67%)

0 / 6 (0.00%)

0 / 1 (0.00%)

1 / 7 (14.29%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Haemoptysis

subjects affected / exposed

0 / 4 (0.00%)

1 / 7 (14.29%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pleural effusion

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

1 / 7 (14.29%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

1 / 9 (11.11%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonitis

subjects affected / exposed

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 8 (12.50%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumothorax

subjects affected / exposed

0 / 4 (0.00%)

1 / 7 (14.29%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

1 / 7 (14.29%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary haemorrhage

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

1 / 9 (11.11%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Stridor

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Confusional state

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Delirium

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 1 (100.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

Alanine aminotransferase increased

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 1 (100.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Aspartate aminotransferase increased

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 1 (100.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood bilirubin increased

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood creatinine increased

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Platelet count decreased

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Gastroenteritis radiation

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infusion related reaction

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

1 / 10 (10.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Procedural pain

subjects affected / exposed

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Cardiac arrest

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

1 / 7 (14.29%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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

Cardiac tamponade

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 8 (12.50%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Myocardial infarction

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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

Pericardial effusion

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Supraventricular tachycardia

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 6 (16.67%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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

Bell's palsy

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

1 / 9 (11.11%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Brain oedema

subjects affected / exposed

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

1 / 7 (14.29%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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

Cerebrovascular accident

subjects affected / exposed

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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

Hemiparesis

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

1 / 7 (14.29%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Secondary cerebellar degeneration

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Seizure

subjects affected / exposed

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

1 / 8 (12.50%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

1 / 8 (12.50%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Febrile neutropenia

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neutropenia

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

1 / 4 (25.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal pain

subjects affected / exposed

1 / 4 (25.00%)

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

1 / 10 (10.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

2 / 12 (16.67%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Constipation

subjects affected / exposed

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Diarrhoea

subjects affected / exposed

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 8 (12.50%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 1 (100.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

1 / 9 (11.11%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Duodenitis

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal haemorrhage

subjects affected / exposed

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 8 (12.50%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 6 (16.67%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Haematemesis

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

1 / 7 (14.29%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ileus

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 8 (12.50%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intestinal obstruction

subjects affected / exposed

0 / 4 (0.00%)

1 / 7 (14.29%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Intestinal perforation

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 6 (16.67%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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

Large intestinal haemorrhage

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malignant gastrointestinal obstruction

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Melaena

subjects affected / exposed

0 / 4 (0.00%)

1 / 7 (14.29%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nausea

subjects affected / exposed

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 8 (12.50%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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

Pancreatitis

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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 / 4 (0.00%)

1 / 7 (14.29%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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 / 4 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Upper gastrointestinal haemorrhage

subjects affected / exposed

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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

Hepatobiliary disorders

Cholangitis

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

1 / 10 (10.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatic failure

subjects affected / exposed

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 0

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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

Haematuria

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hydronephrosis

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 8 (12.50%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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

Endocrine disorders

Adrenal insufficiency

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Arthralgia

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Back pain

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

1 / 6 (16.67%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pain in extremity

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psoriatic arthropathy

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Encephalitis

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 1 (100.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Enterocolitis infectious

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Escherichia bacteraemia

subjects affected / exposed

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infected fistula

subjects affected / exposed

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

1 / 9 (11.11%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

1 / 8 (12.50%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 8 (12.50%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

2 / 7 (28.57%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Sepsis

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 8 (12.50%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Septic shock

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

1 / 2 (50.00%)

0 / 1 (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

Skin infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Soft tissue infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary tract infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

2 / 18 (11.11%)

0 / 8 (0.00%)

0 / 10 (0.00%)

1 / 4 (25.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

1 / 1 (100.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Cachexia

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

1 / 9 (11.11%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Decreased appetite

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dehydration

subjects affected / exposed

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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

Hypocalcaemia

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 18 (5.56%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypoglycaemia

subjects affected / exposed

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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 / 4 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 18 (0.00%)

0 / 8 (0.00%)

0 / 10 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 1 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 2 (0.00%)

0 / 9 (0.00%)

0 / 2 (0.00%)

0 / 1 (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	BMS-986178 ESC 20 MG	BMS-986178 ESC 40 MG	BMS-986178 ESC 80 MG	BMS-986178 ESC 160 MG	BMS-986178 ESC 320 MG	BMS-986178 ESC 20 MG+NIVO 240 MG	BMS-986178 ESC 80 MG+NIVO 240 MG	BMS-986178 ESC 40 MG+NIVO 240 MG	BMS-986178 ESC 160 MG+NIVO 240 MG	BMS-986178 EXP 80 MG+NIVO 240 MG (BLADDER CANCER)	BMS-986178 ESC 320 MG+NIVO 240 MG	BMS-986178 ESC 40 MG+IPI 1 MG/KG	BMS-986178 ESC 20 MG+IPI 1 MG/KG	BMS-986178 ESC 80 MG+IPI 1 MG/KG	BMS-986178 ESC 160 MG+IPI 1 MG/KG	BMS-986178 EPL 80 MG+NIVO 480 MG	BMS-986178 ESC 320 MG+IPI 1 MG/KG	BMS-986178 EPL 80 MG+IPI 3 MG/KG	BMS-986178 EXP 40 MG+NIVO 240/480 MG+IPI 1 MG/KG (RCC)	BMS-986178 SAF 40 MG+NIVO 240/480 MG+IPI 1 MG/KG (RCC)	BMS-986178 SAF 40 MG+NIVO 240 MG+IPI 1 MG/KG (NSCLC)	BMS-986178 EPL 20 MG+NIVO 480 MG (BLADDER CANCER)	NIVO 480 MG EPL (BLADDER CANCER)	BMS-986178 EPL 40 MG+NIVO 480 MG (BLADDER CANCER)	BMS-986178 EXP 40 MG+NIVO 240 MG+IPI 1 MG/KG (NSCLC)	BMS-986178 EPL 80 MG+NIVO 480 MG (BLADDER CANCER)	BMS-986178 EXP 40 MG+NIVO 480 MG+DPV 1
Total subjects affected by non serious adverse events
subjects affected / exposed	4 / 4 (100.00%)	4 / 4 (100.00%)	4 / 4 (100.00%)	3 / 4 (75.00%)	4 / 4 (100.00%)	7 / 7 (100.00%)	12 / 12 (100.00%)	8 / 8 (100.00%)	6 / 8 (75.00%)	18 / 18 (100.00%)	8 / 8 (100.00%)	10 / 10 (100.00%)	4 / 4 (100.00%)	7 / 7 (100.00%)	8 / 8 (100.00%)	11 / 12 (91.67%)	6 / 6 (100.00%)	6 / 6 (100.00%)	1 / 1 (100.00%)	5 / 7 (71.43%)	6 / 6 (100.00%)	2 / 2 (100.00%)	2 / 2 (100.00%)	2 / 2 (100.00%)	9 / 9 (100.00%)	2 / 2 (100.00%)	1 / 1 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphangiosis carcinomatosa
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Malignant neoplasm progression
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Metastases to central nervous system
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Tumour pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	4	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Embolism
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Embolism venous
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Hot flush
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Hypertension
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 8 (0.00%)	2 / 18 (11.11%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	3	1	0	2	1	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Hypotension
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 1 (0.00%)	1 / 7 (14.29%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0	0	0	2	0	0	0	0	0	0	0	0	1	1	0	2	1	0	0	0	0	0	0
Phlebitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Thrombophlebitis superficial
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 8 (0.00%)	1 / 18 (5.56%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	2 / 8 (25.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	2 / 6 (33.33%)	1 / 2 (50.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	3 / 9 (33.33%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	1	1	3	0	1	3	0	0	1	5	0	0	0	0	0	4	2	1	0	7	0	0
Axillary pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Chest discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Chest pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Chills
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 7 (28.57%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	1 / 18 (5.56%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	3 / 6 (50.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	0	0	0	0	2	0	0	1	1	0	1	0	0	0	1	0	3	0	1	2	0	0	2	0	0	1
Early satiety
subjects affected / exposed	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Fatigue
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	2 / 12 (16.67%)	1 / 8 (12.50%)	5 / 8 (62.50%)	7 / 18 (38.89%)	4 / 8 (50.00%)	2 / 10 (20.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	2 / 8 (25.00%)	3 / 12 (25.00%)	2 / 6 (33.33%)	4 / 6 (66.67%)	1 / 1 (100.00%)	3 / 7 (42.86%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	4 / 9 (44.44%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	1	1	2	1	6	9	5	3	0	1	5	3	2	5	1	5	2	0	0	2	7	2	0
Feeling cold
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gait disturbance
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	2 / 8 (25.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Influenza like illness
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Injury associated with device
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Localised oedema
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Malaise
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Mass
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Mucosal inflammation
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Nodule
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Non-cardiac chest pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Oedema peripheral
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	2 / 12 (16.67%)	1 / 8 (12.50%)	0 / 8 (0.00%)	4 / 18 (22.22%)	1 / 8 (12.50%)	0 / 10 (0.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	2 / 8 (25.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 9 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	1	0	1	0	0	0	2	1	0	5	1	0	1	2	3	0	0	0	0	0	0	0	0	1	0	1	0
Pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	2	1	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Pyrexia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	2 / 7 (28.57%)	5 / 12 (41.67%)	2 / 8 (25.00%)	0 / 8 (0.00%)	4 / 18 (22.22%)	2 / 8 (25.00%)	4 / 10 (40.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	3 / 12 (25.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 9 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	3	4	2	5	3	0	4	2	4	1	0	1	4	0	0	0	1	0	1	0	1	0	2	0
Swelling face
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Temperature regulation disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Immune system disorders
Allergy to arthropod sting
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Seasonal allergy
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Reproductive system and breast disorders
Breast pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0
Pelvic pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Scrotal oedema
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Scrotal pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vaginal discharge
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Bronchospasm
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Cough
subjects affected / exposed	1 / 4 (25.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	2 / 4 (50.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 8 (12.50%)	2 / 18 (11.11%)	2 / 8 (25.00%)	1 / 10 (10.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	2 / 6 (33.33%)	1 / 6 (16.67%)	1 / 1 (100.00%)	1 / 7 (14.29%)	1 / 6 (16.67%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	4 / 9 (44.44%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	1	2	1	1	2	0	1	0	1	2	3	2	1	0	0	0	3	1	1	1	2	1	0	0	6	1	0
Dysphonia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dyspnoea
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	2 / 12 (16.67%)	0 / 8 (0.00%)	2 / 8 (25.00%)	1 / 18 (5.56%)	1 / 8 (12.50%)	2 / 10 (20.00%)	0 / 4 (0.00%)	2 / 7 (28.57%)	0 / 8 (0.00%)	4 / 12 (33.33%)	1 / 6 (16.67%)	2 / 6 (33.33%)	1 / 1 (100.00%)	2 / 7 (28.57%)	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	5 / 9 (55.56%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	1	1	2	0	2	2	1	2	0	2	0	4	1	2	1	2	1	0	1	0	10	1	0
Dyspnoea exertional
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	2	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0
Epistaxis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Haemoptysis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	3 / 9 (33.33%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0	1	0	0	0	0	0	0	0	3	0	0
Hiccups
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hypoxia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Nasal congestion
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Oropharyngeal pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0
Pleural effusion
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	2	0	0
Pleuritic pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0
Pneumothorax
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Productive cough
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	1 / 18 (5.56%)	1 / 8 (12.50%)	1 / 10 (10.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	1	1	1	0	1	0	0	0	0	0	0	0	0	0	0	1	1	0
Pulmonary embolism
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0
Pulmonary haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Respiratory tract congestion
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Rhinitis allergic
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Sinus congestion
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0
Wheezing
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 7 (28.57%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Psychiatric disorders
Affect lability
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Anxiety
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 9 (22.22%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	1	1	0	0	2	0	0	0	1	0	0	1	0	1	0	0	0	0	2	1	0
Bradyphrenia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Confusional state
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Depression
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Insomnia
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	2 / 6 (33.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	1	0	0	2	0	0	0	3	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 12 (8.33%)	2 / 8 (25.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	2 / 4 (50.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	1	1	2	0	0	0	0	2	0	0	1	0	1	0	0	0	0	0	0	0	0	0
Ammonia increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Amylase increased
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 8 (0.00%)	3 / 18 (16.67%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	4	0	0	0	1	2	0	5	0	1	0	0	0	1	0	0	0	0	2	0	5	0	0	0	0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 4 (0.00%)	2 / 4 (50.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 12 (8.33%)	2 / 8 (25.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	2 / 4 (50.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	2	0	1	0	1	2	3	1	0	0	0	2	0	0	1	0	0	0	0	1	0	0	0	0	0	0
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	3 / 7 (42.86%)	1 / 12 (8.33%)	2 / 8 (25.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	2 / 7 (28.57%)	1 / 8 (12.50%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	1	0	3	1	2	0	0	0	0	0	2	1	0	1	0	0	0	1	0	0	0	0	0	0
Blood bilirubin increased
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	3 / 8 (37.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 1 (100.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	3	0	0	0	0	1	4	0	0	0	0	0	0	0	0	0	0	3	0	0	0	6	0	0	0	0
Blood chloride decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Blood chloride increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood creatinine increased
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	2 / 12 (16.67%)	1 / 8 (12.50%)	0 / 8 (0.00%)	5 / 18 (27.78%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	1 / 12 (8.33%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0	0	2	1	0	6	0	0	0	0	5	2	1	7	0	0	1	0	0	0	2	0	0
Blood glucose increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood lactic acid increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Blood phosphorus decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood thyroid stimulating hormone decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Blood thyroid stimulating hormone increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood urea increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	2	0	0	0	0	0	0	0	0	0
Carbon dioxide decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Creatinine renal clearance decreased
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	2 / 18 (11.11%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Glomerular filtration rate decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0	0	0	0	0
Lipase increased
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	3 / 18 (16.67%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0	0	0	2	0	7	0	1	0	0	0	1	0	0	0	0	3	0	3	0	0	0	0
Lymph node palpable
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Lymphocyte count decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Neutrophil count decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 8 (12.50%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	2	2	0	0	0	0	0	2	1	0	1	0	0	0	0	0	0	0	0	0	0
Neutrophil count increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0
Platelet count decreased
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 7 (28.57%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0	2	0	2	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Platelet count increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Serum ferritin decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Urine output decreased
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Urine protein/creatinine ratio increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Weight decreased
subjects affected / exposed	1 / 4 (25.00%)	2 / 4 (50.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	1 / 8 (12.50%)	2 / 18 (11.11%)	0 / 8 (0.00%)	2 / 10 (20.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	2 / 8 (25.00%)	0 / 12 (0.00%)	2 / 6 (33.33%)	1 / 6 (16.67%)	1 / 1 (100.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	1 / 9 (11.11%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	1	2	0	0	0	0	3	0	2	2	0	3	1	0	2	0	2	1	1	0	2	0	0	1	1	2	0
Weight increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
White blood cell count decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
White blood cell count increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Contusion
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Fall
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Infusion related reaction
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	3 / 8 (37.50%)	1 / 12 (8.33%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	2 / 6 (33.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	5	1	2	0	0	0	4	0	0	0	2	0	0
Muscle strain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Post procedural haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Procedural pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0
Thermal burn
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Vascular access complication
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vascular access site occlusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Cardiac disorders
Arrhythmia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 1 (100.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Atrial fibrillation
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Cardiac failure
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Palpitations
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Sinus tachycardia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Supraventricular tachycardia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Tachycardia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Nervous system disorders
Aphasia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Balance disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Bell's palsy
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Disturbance in attention
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Dizziness
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	3 / 8 (37.50%)	2 / 18 (11.11%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	3	2	0	0	0	0	1	0	0	0	0	0	0	0	0	2	0	0	0
Dysgeusia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 1 (100.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0
Head discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Headache
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 8 (0.00%)	1 / 18 (5.56%)	2 / 8 (25.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0	1	1	1	0	1	2	1	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0
Hypoaesthesia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Lethargy
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Memory impairment
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Migraine
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Neuralgia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0
Neuropathy peripheral
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	3	0	0	0	1	0	2	1	0	0	0	0	0	0	0	0	0
Peripheral sensory neuropathy
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Presyncope
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Sciatica
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Secondary cerebellar degeneration
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Taste disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Tremor
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 9 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	2	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	2 / 4 (50.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	3 / 7 (42.86%)	2 / 12 (16.67%)	4 / 8 (50.00%)	1 / 8 (12.50%)	8 / 18 (44.44%)	1 / 8 (12.50%)	3 / 10 (30.00%)	0 / 4 (0.00%)	2 / 7 (28.57%)	3 / 8 (37.50%)	5 / 12 (41.67%)	2 / 6 (33.33%)	2 / 6 (33.33%)	0 / 1 (0.00%)	2 / 7 (28.57%)	1 / 6 (16.67%)	0 / 2 (0.00%)	2 / 2 (100.00%)	1 / 2 (50.00%)	3 / 9 (33.33%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	7	0	0	4	8	8	3	16	2	3	0	4	8	13	5	2	0	4	3	0	3	2	3	0	0
Lymph node pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Lymphadenopathy
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Neutropenia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0
Thrombocytopenia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Tinnitus
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vertigo
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Eye disorders
Blepharospasm
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cataract
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Conjunctivitis allergic
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dry eye
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Eye irritation
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Eye pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0
Eyelid rash
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Lacrimation increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Macular degeneration
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Ocular hyperaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Periorbital oedema
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Vision blurred
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	1	0	0	0	0	1	0	0
Vitreous floaters
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Abdominal distension
subjects affected / exposed	2 / 4 (50.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	1 / 1 (100.00%)
occurrences all number	3	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Abdominal pain
subjects affected / exposed	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	2 / 4 (50.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	2 / 12 (16.67%)	2 / 8 (25.00%)	2 / 8 (25.00%)	3 / 18 (16.67%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 8 (12.50%)	2 / 12 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	2 / 9 (22.22%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	1	1	0	3	0	1	2	2	4	3	0	1	0	1	1	6	1	0	0	1	0	0	1	0	2	1	0
Abdominal pain lower
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Abdominal pain upper
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Anal haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Anorectal discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Aphthous ulcer
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Ascites
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	1 / 1 (100.00%)
occurrences all number	1	0	0	0	0	0	0	0	3	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1
Constipation
subjects affected / exposed	1 / 4 (25.00%)	1 / 4 (25.00%)	2 / 4 (50.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	4 / 12 (33.33%)	2 / 8 (25.00%)	3 / 8 (37.50%)	3 / 18 (16.67%)	1 / 8 (12.50%)	5 / 10 (50.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	2 / 12 (16.67%)	3 / 6 (50.00%)	2 / 6 (33.33%)	0 / 1 (0.00%)	0 / 7 (0.00%)	2 / 6 (33.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	2 / 2 (100.00%)	0 / 1 (0.00%)
occurrences all number	1	1	2	1	0	1	6	2	4	4	1	5	1	0	0	2	4	2	0	0	2	0	0	0	1	2	0
Diarrhoea
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 8 (25.00%)	4 / 18 (22.22%)	0 / 8 (0.00%)	2 / 10 (20.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	2 / 8 (25.00%)	2 / 12 (16.67%)	2 / 6 (33.33%)	1 / 6 (16.67%)	1 / 1 (100.00%)	3 / 7 (42.86%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	2 / 9 (22.22%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	2	1	1	1	2	0	0	5	6	0	2	0	1	5	2	5	1	2	3	1	0	0	1	8	1	0
Diverticulum
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dry mouth
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	1	0	0	0	1	0	0	0	2	0
Dyspepsia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dysphagia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Flatulence
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 1 (100.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0	0	3	0	0	0	1	0	0	0	1	0	0	0	1	0	1	0	0	0	0	0	0
Glossodynia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Haemorrhoids
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Large intestinal haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Mouth haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Nausea
subjects affected / exposed	3 / 4 (75.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	2 / 7 (28.57%)	3 / 12 (25.00%)	1 / 8 (12.50%)	2 / 8 (25.00%)	0 / 18 (0.00%)	2 / 8 (25.00%)	2 / 10 (20.00%)	1 / 4 (25.00%)	2 / 7 (28.57%)	2 / 8 (25.00%)	3 / 12 (25.00%)	0 / 6 (0.00%)	4 / 6 (66.67%)	1 / 1 (100.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	3	0	1	1	2	2	3	1	6	0	3	2	2	2	2	3	0	6	1	1	0	1	0	0	1	0	0
Odynophagia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Oral pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Rectal haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Retching
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Small intestinal obstruction
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Stomatitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 1 (100.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Swollen tongue
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vomiting
subjects affected / exposed	2 / 4 (50.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	2 / 12 (16.67%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	2 / 8 (25.00%)	2 / 10 (20.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	1 / 8 (12.50%)	2 / 12 (16.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 1 (0.00%)	1 / 7 (14.29%)	1 / 6 (16.67%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	2	0	0	1	0	1	2	0	4	0	2	4	3	1	2	2	1	2	0	1	1	1	0	0	1	3	0
Hepatobiliary disorders
Biliary obstruction
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cholelithiasis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hyperbilirubinaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Autoimmune dermatitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0
Dry skin
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1	0	0	1	0	1	0	0	0	0	0	0	0	0	1	0	0
Eczema
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Erythema
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Hyperhidrosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hyperkeratosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Nail disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Pruritus
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 7 (28.57%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	2 / 18 (11.11%)	0 / 8 (0.00%)	3 / 10 (30.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	1 / 8 (12.50%)	3 / 12 (25.00%)	2 / 6 (33.33%)	3 / 6 (50.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	5 / 9 (55.56%)	2 / 2 (100.00%)	0 / 1 (0.00%)
occurrences all number	0	2	0	0	0	2	0	0	1	2	0	3	1	1	1	4	2	5	0	2	2	0	1	0	11	2	0
Psoriasis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Rash
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	1 / 18 (5.56%)	0 / 8 (0.00%)	2 / 10 (20.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 1 (0.00%)	1 / 7 (14.29%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 9 (22.22%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	2	0	4	3	0	0	3	0	1	1	0	0	0	4	0	0
Rash erythematous
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Rash maculo-papular
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	1	1	0
Rash papular
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Rash pruritic
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Skin disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Skin haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Skin ulcer
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dysuria
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Haematuria
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	2 / 18 (11.11%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	3	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0
Micturition urgency
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Nephritis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Pollakiuria
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Proteinuria
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Renal disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	2 / 18 (11.11%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Renal failure
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0
Urinary incontinence
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Urinary retention
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 1 (100.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	1	0	0	0	0	0	0	0	0
Hypothyroidism
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	2 / 8 (25.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	2	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0
Thyroiditis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	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 / 4 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 12 (8.33%)	1 / 8 (12.50%)	2 / 8 (25.00%)	2 / 18 (11.11%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	2 / 12 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	1 / 2 (50.00%)	1 / 2 (50.00%)	3 / 9 (33.33%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	2	0	0	1	1	2	5	3	0	0	0	2	0	3	1	0	0	0	1	0	2	1	10	0	0
Arthritis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	2	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Back pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 8 (12.50%)	3 / 18 (16.67%)	2 / 8 (25.00%)	1 / 10 (10.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	2 / 6 (33.33%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	1	1	0	4	7	2	1	1	0	1	0	2	1	0	0	2	0	0	0	0	2	0
Bone pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Bursitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Flank pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	1 / 18 (5.56%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	1	0	0	0	3	0	1	0	0	0	0	0	0	0	0	0
Joint range of motion decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Joint stiffness
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Muscle spasms
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	3 / 8 (37.50%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	6	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Muscle twitching
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Muscular weakness
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 9 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	1	0	1	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 9 (22.22%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	1	0	0	0	1	2	0	0	5	0	0
Musculoskeletal discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0	0
Myalgia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1
Neck pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Pain in extremity
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 8 (12.50%)	3 / 18 (16.67%)	1 / 8 (12.50%)	0 / 10 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	4	1	0	1	0	0	0	0	0	0	0	1	1	0	0	2	0	0
Psoriatic arthropathy
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0	0	0	0	0	0	0
Rotator cuff syndrome
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0	0	0	0	0	0
Spinal pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	3	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0
Weight bearing difficulty
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Infections and infestations
Abdominal infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Bronchitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	3	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Candida infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cellulitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cryptosporidiosis infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cystitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Ear infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Erysipelas
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Escherichia sepsis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Fungal infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Gastroenteritis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gingivitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Nail infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	2 / 8 (25.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	1	1	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0
Oral candidiasis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0
Oral herpes
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Peritonitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Pharyngitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Pharyngitis streptococcal
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Pneumonia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	2 / 12 (16.67%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	3	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0
Rash pustular
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory tract infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 9 (22.22%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	3	1	0
Sepsis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Sinusitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Skin infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Sputum purulent
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0	0	0	0	1	0	0	1	0	0	0	0	1	0	0	0	0	2	0	0
Urinary tract infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	2 / 8 (25.00%)	1 / 8 (12.50%)	2 / 18 (11.11%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	2 / 2 (100.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	2	1	2	0	0	0	0	0	0	0	1	0	0	1	0	0	0	1	3	0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Wound infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	2 / 8 (25.00%)	3 / 18 (16.67%)	7 / 8 (87.50%)	2 / 10 (20.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	3 / 8 (37.50%)	1 / 12 (8.33%)	2 / 6 (33.33%)	3 / 6 (50.00%)	1 / 1 (100.00%)	0 / 7 (0.00%)	3 / 6 (50.00%)	1 / 2 (50.00%)	1 / 2 (50.00%)	1 / 2 (50.00%)	2 / 9 (22.22%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	1	0	1	2	0	0	1	1	2	4	9	2	1	0	4	1	3	4	1	0	3	1	1	3	2	1	0
Dehydration
subjects affected / exposed	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 8 (12.50%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 1 (100.00%)	0 / 7 (0.00%)	2 / 6 (33.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	1	0	0	0	0	2	1	0	0	0	0	0	1	1	0	0	2	1	0	3	0	0	0	0	0	0
Diabetes mellitus
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gout
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0	0	0	0	0	0
Hypercalcaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	2 / 12 (16.67%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	2	1	0	0	0	0	0	0	1	4	0	0	0	0	0	1	0	0	0	0	0
Hyperglycaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 12 (8.33%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 1 (100.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	3	1	0	1	0	0	0	0	0	0	0	0
Hyperkalaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	2 / 8 (25.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	1 / 8 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	4	3	0	1	9	0	0	0	0	0	0	6	0	0	0	0	0	0	0	0	0
Hypernatraemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Hyperuricaemia
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hypoalbuminaemia
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	2 / 8 (25.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	2 / 7 (28.57%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0	0	0	3	0	3	0	0	0	2	0	0	0	2	0	0	0	0	0	0	0	0	0
Hypocalcaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Hypoglycaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hypokalaemia
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	2 / 8 (25.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 9 (11.11%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0	0	1	0	1	0	0	2	1	0	0	0	0	0	0	0	0	3	0	0
Hypomagnesaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	2 / 6 (33.33%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	2	1	1	0	0	0	1	0	0	5	1	0	0	0	0	2	0	1	0	0	0	0
Hyponatraemia
subjects affected / exposed	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 8 (12.50%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 1 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	1 / 2 (50.00%)	0 / 1 (0.00%)
occurrences all number	1	1	0	0	0	0	2	1	0	0	0	0	0	1	1	1	0	2	0	0	1	0	0	0	0	4	0
Hypophosphataemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	1 / 18 (5.56%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 1 (100.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	2	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0
Type 2 diabetes mellitus
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 18 (0.00%)	0 / 8 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 1 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 9 (0.00%)	0 / 2 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

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Were there any global substantial amendments to the protocol? Yes

23 Nov 2016

Removal of Part 1B. Addition of Part 2D, 2E, 3C and Part 2A cohort dose -1

04 Apr 2017

Addition of Parts 4, 5, 6, and 7. Update of inclusion and exclusion criteria to include the new parts and clarify the maximum number of prior treatments allowed

11 Dec 2017

Addition of Part 8

22 Jun 2018

Incorporates DRibble vaccine (DPV-001) as a new combination with BMS 986178 in Part 9

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Phase 1/2a Study of BMS-986178 Administered Alone or in Combination with Nivolumab and/or Ipilimumab in Subjects with Advanced Solid Tumors

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: The number of Participants Experiencing Adverse Events (AEs)

Primary: The number of Participants Experiencing Adverse Events (AEs)

Primary: The Number of Participants Experiencing Serious Adverse Events (SAEs)

Primary: The Number of Participants Experiencing Serious Adverse Events (SAEs)

Primary: The Number of Participants with Clinical Laboratory Test Abnormalities (Hematology)

Primary: The Number of Participants with Clinical Laboratory Test Abnormalities (Hematology)

Primary: The Number of Participants with Clinical Laboratory Test Abnormalities (LIVER AND KIDNEY FUNCTION)

Primary: The Number of Participants with Clinical Laboratory Test Abnormalities (LIVER AND KIDNEY FUNCTION)

Primary: The Number of Participants with Clinical Laboratory Test Abnormalities (OTHER CHEMISTRY TESTING )

Primary: The Number of Participants with Clinical Laboratory Test Abnormalities (OTHER CHEMISTRY TESTING )

Primary: The number of Participants Experiencing Dose-Limiting Toxicities (DLTs)

Primary: The number of Participants Experiencing Dose-Limiting Toxicities (DLTs)

Primary: The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation

Primary: The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation

Primary: The Number of Participant Deaths

Primary: The Number of Participant Deaths

Secondary: Objective Response Rate (ORR)

Secondary: Objective Response Rate (ORR)

Secondary: Duration of Response (DOR)

Secondary: Duration of Response (DOR)

Secondary: Progression Free Survival (PFS) Rate at 24 Weeks

Secondary: Progression Free Survival (PFS) Rate at 24 Weeks

Secondary: Cmax: Maximum observed serum concentration

Secondary: Cmax: Maximum observed serum concentration

Secondary: Tmax: Time of maximum observed serum concentration

Secondary: Tmax: Time of maximum observed serum concentration

Secondary: AUC(0-t): Area under the serum concentration-time curve from time 0 to time t

Secondary: AUC(0-t): Area under the serum concentration-time curve from time 0 to time t

Secondary: AUC(TAU): Area under the serum concentration-time curve in 1 dosing interval

Secondary: AUC(TAU): Area under the serum concentration-time curve in 1 dosing interval

Secondary: Ctau: Observed serum concentration at the end of a dosing interval when intensive samples are collected

Secondary: Ctau: Observed serum concentration at the end of a dosing interval when intensive samples are collected

Secondary: CLT: Total body clearance

Secondary: CLT: Total body clearance

Secondary: Css-avg: Average concentration over a dosing interval (AUC(TAU)/tau)

Secondary: Css-avg: Average concentration over a dosing interval (AUC(TAU)/tau)

Secondary: AI: Accumulation Index. Ratio of an exposure measure at steady state (Cmax)

Secondary: AI: Accumulation Index. Ratio of an exposure measure at steady state (Cmax)

Secondary: AI: Accumulation Index. Ratio of an exposure measure at steady state (AUC)

Secondary: AI: Accumulation Index. Ratio of an exposure measure at steady state (AUC)

Secondary: AI: Accumulation Index. Ratio of an exposure measure at steady state (Ctau)

Secondary: AI: Accumulation Index. Ratio of an exposure measure at steady state (Ctau)

Secondary: T-HALFeff: Effective elimination half-life that explains the degree of accumulation observed for a specific exposure measure (exposure measure includes AUC(TAU), Cmax)

Secondary: T-HALFeff: Effective elimination half-life that explains the degree of accumulation observed for a specific exposure measure (exposure measure includes AUC(TAU), Cmax)

Secondary: Ctrough: Trough observed plasma concentration

Secondary: Ctrough: Trough observed plasma concentration

Secondary: Frequency of Positive Anti-Drug Antibodies (ADA) to BMS-986178

Secondary: Frequency of Positive Anti-Drug Antibodies (ADA) to BMS-986178

Secondary: Frequency of Positive Anti-Drug Antibodies (ADA) to Nivolumab

Secondary: Frequency of Positive Anti-Drug Antibodies (ADA) to Nivolumab

Secondary: Frequency of Positive Anti-Drug Antibodies (ADA) to Ipilimumab.

Secondary: Frequency of Positive Anti-Drug Antibodies (ADA) to Ipilimumab.

Secondary: The Number of Participants Showing a Change in Soluble OX40 and Peripheral OX40 Receptor Occupancy Pharmacodynamic Biomarkers in Part 8

Secondary: The Number of Participants Showing a Change in Soluble OX40 and Peripheral OX40 Receptor Occupancy Pharmacodynamic Biomarkers in Part 8

Secondary: Tumor Pharmacodynamics of BMS-986178 in Combination with Nivolumab or Nivolumab Monotherapy in Part 8

Secondary: Tumor Pharmacodynamics of BMS-986178 in Combination with Nivolumab or Nivolumab Monotherapy in Part 8

Secondary: The number of Participants with Sustained T Cell Expansion with DPV-001 in Combination with Nivolumab or Nivolumab Monotherapy in Part 9

Secondary: The number of Participants with Sustained T Cell Expansion with DPV-001 in Combination with Nivolumab or Nivolumab Monotherapy in Part 9

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 1/2a Study of BMS-986178 Administered Alone or in Combination with Nivolumab and/or Ipilimumab in Subjects with Advanced Solid Tumors