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Clinical Trial Results:
A Dose-Ranging Study of the Efficacy and Safety of Bardoxolone Methyl in Patients with Pulmonary Hypertension (PH) - LARIAT

Summary
EudraCT number	2016-004793-17
Trial protocol	DE GB ES
Global end of trial date	16 May 2018

Results information
Results version number	v1(current)
This version publication date	01 Dec 2021
First version publication date	01 Dec 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

402-C-1302

ISRCTN number

US NCT number

NCT02036970

WHO universal trial number (UTN)

Sponsor organisation name

Reata Pharmaceuticals, Inc.

Sponsor organisation address

5320 Legacy Drive, Plano, United States, 75024

Public contact

Kris Loerwald, Reata Pharmaceuticals, Inc., 972 865-2219, MedicalAffairs-Team@reatapharma.com

Scientific contact

Kris Loerwald, Reata Pharmaceuticals, Inc., 972 865-2219, MedicalAffairs-Team@reatapharma.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

17 Dec 2020

Is this the analysis of the primary completion data?

Yes

Primary completion date

19 Jan 2018

Global end of trial reached?

Yes

Global end of trial date

16 May 2018

Was the trial ended prematurely?

Main objective of the trial

This study assesses the safety and efficacy of bardoxolone methyl relative to placebo in patients with pulmonary hypertension to determine the recommended dose range, evaluate the change from baseline in 6-minute walk distance (6MWD) and determine the effect of Bardoxolone methyl in pulmonary hypertension associated with connective tissue disease, interstitial lung disease, and idiopathic etiologies, including subsets of patients with WHO Group III or WHO Group V PH following 16 weeks of study participation.

Protection of trial subjects

A Protocol Safety Review Committee (PSRC) assessed the starting dose and each new dose level of bardoxolone methyl for safety and tolerability based on review of all available data for this study at the time of each review. PSRC reviews occurred after the Week 4 data are available for the first eight patients enrolled at each new dose level combined across Cohorts 1 and 2 (i.e., the 6MWD ≤ 450 m and 6MWD > 450 m cohorts). Upon completion of the dose ranging portion of the study, the PSRC continued to meet at regular intervals (approximately quarterly) to monitor safety of all patients, including those enrolled in Cohorts 3 and 4. The PSRC included at a minimum a Sponsor representative, a cardiologist, and a statistician. PSRC also assessed for general safety and specific signs and symptoms of fluid overload. The PSRC assessment included a dose level recommendation based on clinical evaluation of protocol specified assessments for subsequent cohorts to escalate to a higher dose, proceed to a lower dose, or maintain the current dose. The PSRC also could recommend stopping dosing in current cohorts.

Background therapy

Evidence for comparator

Actual start date of recruitment

01 Jun 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 164

Country: Number of subjects enrolled

Germany: 2

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)

124

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Part 1: 16-week double-blind, randomized, placebo-controlled treatment period (Day 1 to Week 16). Part 2: Open-label extension period (Week 16 onwards). Part 2 is the extension period and patients were to stay until study drug became available through extended access program [Study 402-C-1602]. Each participant in Part 2 was also in Part 1.

Period 1 title

Part 1: Day 1 Through Week 16

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Subject

Are arms mutually exclusive

Yes

Part 1:Dose Ranging Bardoxolone Methyl 2.5mg

Arm description

Participants received bardoxolone methyl 2.5 mg once-daily in Part 1 (Day 1 to Week 16). Participants who continued to Part 2 continued to receive the same bardoxolone methyl 2.5 mg once-daily in Part 2 (Week 16 and onwards)

Arm type

Experimental

Investigational medicinal product name

Bardoxolone methyl capsules 2.5mg

Investigational medicinal product code

RTA 402

Other name

RTA 402 capsules

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 1:Dose-Ranging Bardoxolone Methyl 5mg

Arm description

Participants received bardoxolone methyl 5 mg once-daily in Part 1 (Day 1 to Week 16). Participants who continued to Part 2 continued to receive the same bardoxolone methyl 5 mg once-daily in Part 2 (Week 16 and onwards)

Arm type

Experimental

Investigational medicinal product name

Bardoxolone methyl capsules 5mg

Investigational medicinal product code

RTA 402

Other name

RTA 402 capsules

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 1:Dose-Ranging Bardoxolone Methyl 10mg

Arm description

Participants received bardoxolone methyl 10 mg once-daily in Part 1 (Day 1 to Week 16). Participants who continued to Part 2 continued to receive the same bardoxolone methyl 10 mg once-daily in Part 2 (Week 16 and onwards)

Arm type

Experimental

Investigational medicinal product name

Bardoxolone methyl capsules 10mg

Investigational medicinal product code

RTA 402

Other name

RTA 402 capsules

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 1:Dose-Ranging Bardoxolone Methyl 20mg

Arm description

Participants received bardoxolone methyl 20 mg once-daily in Part 1 (Day 1 to Week 16). Participants who continued to Part 2 continued to receive the same bardoxolone methyl 20 mg once-daily in Part 2 (Week 16 and onwards)

Arm type

Experimental

Investigational medicinal product name

Bardoxolone methyl capsules 20mg

Investigational medicinal product code

RTA 402

Other name

RTA 402 capsules

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 1:Dose-Ranging Placebo 2.5mg

Arm description

Participants received bardoxolone methyl 2.5 mg matching placebo capsules once-daily in Part 1 (Day 1 to Week 16). Participants who continued to Part 2 received bardoxolone methyl 2.5 mg once-daily in Part 2 (Week 16 and onwards)

Arm type

Placebo

Investigational medicinal product name

Placebo Capsules

Investigational medicinal product code

Placebo

Other name

Placebo

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 1: Dose-Ranging Placebo 5 mg

Arm description

Participants received bardoxolone methyl 5 mg matching placebo capsules once-daily in Part 1 (Day 1 to Week 16). Participants who continued to Part 2 received bardoxolone methyl 5 mg once-daily in Part 2 (Week 16 and onwards)

Arm type

Placebo

Investigational medicinal product name

Placebo Capsules 5mg

Investigational medicinal product code

Placebo

Other name

Placebo

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 1: Dose-Ranging Placebo 10 mg

Arm description

Participants received bardoxolone methyl 10 mg matching placebo capsules once-daily in Part 1 (Day 1 to Week 16). Participants who continued to Part 2 received bardoxolone methyl 10 mg once-daily in Part 2 (Week 16 and onwards)

Arm type

Placebo

Investigational medicinal product name

Placebo Capsules 10mg

Investigational medicinal product code

Placebo

Other name

Placebo

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 1: Dose-Ranging Placebo 20 mg

Arm description

Participants received bardoxolone methyl 20 mg matching placebo capsules once-daily in Part 1 (Day 1 to Week 16). Participants who continued to Part 2 received bardoxolone methyl 20 mg once-daily in Part 2 (Week 16 and onwards)

Arm type

Placebo

Investigational medicinal product name

Placebo Capsules 20mg

Investigational medicinal product code

Placebo

Other name

Placebo

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 1: Dose Titration: Bardoxolone Methyl 10 mg

Arm description

Participants in Part 1 started with bardoxolone methyl 5 mg once-daily from Day 1 and escalated to bardoxolone methyl 10 mg once-daily starting at Week 4 thru Week 16. Participants who continued to Part 2 continued to receive the same bardoxolone methyl dose once-daily in Part 2 (Week 16 and onwards)

Arm type

Experimental

Investigational medicinal product name

Bardoxolone methyl capsules 10mg

Investigational medicinal product code

RTA 402

Other name

RTA 402 capsules

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 1: Dose Titration: Placebo 10 mg

Arm description

Participants in Part 1 received Placebo once-daily from Day 1 thru Week 16. Participants who continued to Part 2 initially received bardoxolone methyl 5 mg once-daily from Week 16 thru Week 20 and bardoxolone methyl 10 mg from week 20 onwards

Arm type

Placebo

Investigational medicinal product name

Placebo Capsules 10mg

Investigational medicinal product code

Placebo

Other name

Placebo

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 1	Part 1:Dose Ranging Bardoxolone Methyl 2.5mg	Part 1:Dose-Ranging Bardoxolone Methyl 5mg	Part 1:Dose-Ranging Bardoxolone Methyl 10mg	Part 1:Dose-Ranging Bardoxolone Methyl 20mg	Part 1:Dose-Ranging Placebo 2.5mg	Part 1: Dose-Ranging Placebo 5 mg	Part 1: Dose-Ranging Placebo 10 mg	Part 1: Dose-Ranging Placebo 20 mg	Part 1: Dose Titration: Bardoxolone Methyl 10 mg	Part 1: Dose Titration: Placebo 10 mg
Started	6	12	11	12	2	4	3	4	74	38
Completed	5	12	7	9	1	3	3	3	66	33
Not completed	1	0	4	3	1	1	0	1	8	5
Consent withdrawn by subject	-	-	-	-	1	-	-	-	2	4
Adverse event, non-fatal	-	-	3	2	-	1	-	1	3	1
Death	-	-	-	-	-	-	-	-	1	-
Progressive Disease	-	-	-	1	-	-	-	-	-	-
Protocol deviation	1	-	1	-	-	-	-	-	2	-

Period 2 title

Part 2 Open-label extension: Week 16 On

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part 2: Open-Label Bardoxolone Methyl 2.5 mg

Arm description

Arm type

Experimental

Investigational medicinal product name

Bardoxolone methyl capsules 2.5mg

Investigational medicinal product code

RTA 402

Other name

RTA 402 capsules

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 2: Open-Label Bardoxolone Methyl 5 mg

Arm description

Arm type

Experimental

Investigational medicinal product name

Bardoxolone methyl capsules 5mg

Investigational medicinal product code

RTA 402

Other name

RTA 402 capsules

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 2: Open-Label Bardoxolone Methyl 10 mg

Arm description

Arm type

Experimental

Investigational medicinal product name

Bardoxolone methyl capsules 10mg

Investigational medicinal product code

RTA 402

Other name

RTA 402 capsules

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 2: Open-Label Bardoxolone Methyl 20 mg

Arm description

Arm type

Experimental

Investigational medicinal product name

Bardoxolone methyl capsules 20 mg

Investigational medicinal product code

RTA 402

Other name

RTA 402 capsules

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 2: Bardoxolone Methyl 2.5 mg

Arm description

Arm type

Experimental

Investigational medicinal product name

Bardoxolone methyl capsules 2.5mg

Investigational medicinal product code

RTA 402

Other name

RTA 402 capsules

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 2: Bardoxolone Methyl 5 mg

Arm description

Arm type

Experimental

Investigational medicinal product name

Bardoxolone methyl capsules 5mg

Investigational medicinal product code

RTA 402

Other name

RTA 402 capsules

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 2: Bardoxolone Methyl 10 mg

Arm description

Arm type

Experimental

Investigational medicinal product name

Bardoxolone methyl capsules 10mg

Investigational medicinal product code

RTA 402

Other name

RTA 402 capsules

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 2: Bardoxolone Methyl 20 mg

Arm description

Arm type

Experimental

Investigational medicinal product name

Bardoxolone methyl capsules 20mg

Investigational medicinal product code

RTA 402

Other name

RTA 402 capsules

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Part 2: Bardoxolone Methyl 10 mg

Arm description

Arm type

Experimental

Investigational medicinal product name

Bardoxolone methyl capsules 10mg

Investigational medicinal product code

RTA 402

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Bardoxolone methyl capsules 10mg taken orally once daily in Part 2 Open label.

Investigational medicinal product name

Bardoxolone methyl capsules 10mg

Investigational medicinal product code

RTA 402

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Bardoxolone methyl capsules 10mg taken orally once daily in Part 2 (Open label)

Part 2: Bardoxolone methyl capsules 10mg

Arm description

Arm type

Experimental

Investigational medicinal product name

Bardoxolone Methyl 10 mg

Investigational medicinal product code

RTA 402

Other name

RTA 402 capsules

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 2 ^[1]	Part 2: Open-Label Bardoxolone Methyl 2.5 mg	Part 2: Open-Label Bardoxolone Methyl 5 mg	Part 2: Open-Label Bardoxolone Methyl 10 mg	Part 2: Open-Label Bardoxolone Methyl 20 mg	Part 2: Bardoxolone Methyl 2.5 mg	Part 2: Bardoxolone Methyl 5 mg	Part 2: Bardoxolone Methyl 10 mg	Part 2: Bardoxolone Methyl 20 mg	Part 2: Bardoxolone Methyl 10 mg	Part 2: Bardoxolone methyl capsules 10mg
Started	5	11	6	9	1	3	3	3	63	33
Completed	5	6	3	7	0	3	2	2	54	28
Not completed	0	5	3	2	1	0	1	1	9	5
Consent withdrawn by subject	-	1	1	-	-	-	-	-	3	-
Adverse event, non-fatal	-	2	1	1	1	-	1	-	6	3
Progressive Disease	-	2	1	1	-	-	-	-	-	2
Protocol deviation	-	-	-	-	-	-	-	1	-	-

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: 4 Patients total that completed Part 1 of the trial, elected not to continue into Part 2 of the trial therefore, the number of subjects starting the period will not be consistent with the number completing the preceding period.

Baseline characteristics

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Reporting group title

Part 1:Dose Ranging Bardoxolone Methyl 2.5mg

Reporting group description

Reporting group title

Part 1:Dose-Ranging Bardoxolone Methyl 5mg

Reporting group description

Reporting group title

Part 1:Dose-Ranging Bardoxolone Methyl 10mg

Reporting group description

Reporting group title

Part 1:Dose-Ranging Bardoxolone Methyl 20mg

Reporting group description

Reporting group title

Part 1:Dose-Ranging Placebo 2.5mg

Reporting group description

Reporting group title

Part 1: Dose-Ranging Placebo 5 mg

Reporting group description

Reporting group title

Part 1: Dose-Ranging Placebo 10 mg

Reporting group description

Reporting group title

Part 1: Dose-Ranging Placebo 20 mg

Reporting group description

Reporting group title

Part 1: Dose Titration: Bardoxolone Methyl 10 mg

Reporting group description

Reporting group title

Part 1: Dose Titration: Placebo 10 mg

Reporting group description

Reporting group values	Part 1:Dose Ranging Bardoxolone Methyl 2.5mg	Part 1:Dose-Ranging Bardoxolone Methyl 5mg	Part 1:Dose-Ranging Bardoxolone Methyl 10mg	Part 1:Dose-Ranging Bardoxolone Methyl 20mg	Part 1:Dose-Ranging Placebo 2.5mg	Part 1: Dose-Ranging Placebo 5 mg	Part 1: Dose-Ranging Placebo 10 mg	Part 1: Dose-Ranging Placebo 20 mg	Part 1: Dose Titration: Bardoxolone Methyl 10 mg	Part 1: Dose Titration: Placebo 10 mg	Total
Number of subjects	6	12	11	12	2	4	3	4	74	38	166
Age categorical
Units: Subjects
In utero											0
Preterm newborn infants (gestational age < 37 wks)											0
Newborns (0-27 days)											0
Infants and toddlers (28 days-23 months)											0
Children (2-11 years)											0
Adolescents (12-17 years)											0
Adults (18-64 years)											0
From 65-84 years											0
85 years and over											0
Age continuous
Part 1: 16-week double-blind, randomized, placebo-controlled treatment period (Day 1 to Week 16) Part 2: Open-label extension period (Week 16 and onwards
Units: years
arithmetic mean (standard deviation)	52.5 ± 7.15	52.8 ± 14.84	50.6 ± 16.33	49.6 ± 13.06	53 ± 15.56	39.5 ± 11.27	54.7 ± .58	51.3 ± 8.54	56.4 ± 12.41	55.6 ± 12.7	-
Gender categorical
Units: Subjects
Female	4	10	8	11	1	4	2	3	54	27	124
Male	2	2	3	1	1	0	1	1	20	11	42
Ethnicity
Units: Subjects
Hispanic or Latino	2	3	0	1	0	1	0	0	12	7	26
Not Hispanic or Latino	4	9	11	11	2	3	3	4	62	31	140
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0	0
Race
Units: Subjects
American Indian or Alaskan Native	0	0	0	0	0	0	0	0	0	0	0
Asia	0	0	0	0	0	0	0	0	2	0	2
Native Hawaiian or Pacific Islander	0	0	0	0	0	0	0	0	0	1	1
Black or African American	0	1	1	0	0	3	0	0	17	9	31
White	6	11	9	12	2	1	3	4	54	28	130
More than one Race	0	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	1	0	0	0	0	0	1	0	2
6-Minute Walk Test (6MWT)[1]
[1] Measure Analysis Population Description: Modified Intent-to-treat (mITT) population, which included all randomized patients who received at least 28 doses of study treatment, did not undergo heart or lung transplantation during the treatment period, and performed at least one-post baseline 6MWT assessment. Only Part 1 patients are included since the primary outcome is the change from baseline in 6MWD through Week 16
Units: Meters
arithmetic mean (standard deviation)	412 ± 19.7	425.8 ± 81	385.7 ± 55.45	454.5 ± 93.01	358 ± 96.17	418.9 ± 71.18	367 ± 46.02	449.3 ± 84.64	380.8 ± 96.46	395.2 ± 84.99	-

Subject analysis set title

Part 2: Open-Label Bardoxolone Methyl 2.5 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 were eligible to continue to the extension Part 2 and continued to receive the same bardoxolone methyl 2.5 mg once-daily from Week 16 onwards.

Subject analysis set title

Part 2: Open-Label Bardoxolone Methyl 5mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 were eligible to continue to the extension Part 2 and continued to receive the same bardoxolone methyl 5 mg once-daily from Week 16 onwards.

Subject analysis set title

Part 2: Open-Label Bardoxolone Methyl 10 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 wer eligible to continue to the extension Part 2 and continued to receive the same bardoxolone methyl 10 mg once-daily from Week 16 onwards.

Subject analysis set title

Part 2: Open-Label Bardoxolone Methyl 20 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 were eligible to continue to the extension Part 2 and continued to receive the same bardoxolone methyl 20 mg once-daily from Week 16 onwards.

Subject analysis set title

Part 2: Bardoxolone Methyl 2.5 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 were eligible to continue to the extension Part 2 and received bardoxolone methyl 2.5 mg once-daily from Week 16 and onwards.

Subject analysis set title

Part 2: Bardoxolone Methyl 5 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 were eligible to continue to the extension Part 2 and received bardoxolone methyl 5 mg once-daily from Week 16 and onwards.

Subject analysis set title

Part 2: Bardoxolone Methyl 10 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 were eligible to continue to the extension Part 2 and received bardoxolone methyl 10 mg once-daily from Week 16 and onwards.

Subject analysis set title

Part 2: Bardoxolone Methyl 20 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 were eligible to continue to the extension Part 2 and received bardoxolone methyl 20 mg once-daily from Week 16 and onwards.

Subject analysis set title

Part 2: Bardoxolone Methyl 10 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 were eligible to continue to the extension Part 2 and received the same bardoxolone methyl dose once-daily from Week 16 and onwards.

Subject analysis set title

Part 2: Bardoxolone Methyl 10 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 were eligible to continue to the extension Part 2 and initially received bardoxolone methyl 5 mg once-daily from Week 16 thru Week 20 and bardoxolone methyl 10 mg from Week 20 and onwards.

Subject analysis set title

Part 2: Total

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Open-label extension period (Week 16 and onwards)

Subject analysis set title

Change from Baseline though Week 16 for participants with PH

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 1: Dose Titration: Bardoxolone Methyl 10 mg Participants were randomized to receive bardoxolone methyl 10 mg capsules. Participants initially started with bardoxolone methyl 5 mg once-daily from Day 1 and titrated to bardoxolone methyl 10 mg once-daily starting at Week 4 up to Week 16.

Subject analysis set title

Change from Baseline though Week 16 for participants with PH

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 1: Dose Titration: Placebo 10 mg

Subject analysis sets values	Part 2: Open-Label Bardoxolone Methyl 2.5 mg	Part 2: Open-Label Bardoxolone Methyl 5mg	Part 2: Open-Label Bardoxolone Methyl 10 mg	Part 2: Open-Label Bardoxolone Methyl 20 mg	Part 2: Bardoxolone Methyl 2.5 mg	Part 2: Bardoxolone Methyl 5 mg	Part 2: Bardoxolone Methyl 10 mg	Part 2: Bardoxolone Methyl 20 mg	Part 2: Bardoxolone Methyl 10 mg	Part 2: Bardoxolone Methyl 10 mg	Part 2: Total	Change from Baseline though Week 16 for participants with PH	Change from Baseline though Week 16 for participants with PH
Number of subjects	5	11	6	9	1	3	3	3	63	33	137	70	70
Age categorical
Units: Subjects
In utero
Preterm newborn infants (gestational age < 37 wks)
Newborns (0-27 days)
Infants and toddlers (28 days-23 months)
Children (2-11 years)
Adolescents (12-17 years)
Adults (18-64 years)
From 65-84 years
85 years and over
Age continuous
Part 1: 16-week double-blind, randomized, placebo-controlled treatment period (Day 1 to Week 16) Part 2: Open-label extension period (Week 16 and onwards
Units: years
arithmetic mean (standard deviation)	54.6 ± 5.55	53.4 ± 14.4	59.2 ± 10.26	51 ± 14.76	64 ± 0	40 ± 13.75	54.7 ± .58	47.7 ± 5.69	56.5 ± 12.23	56.7 ± 12.44	55.5 ± 12.38	±	±
Gender categorical
Units: Subjects
Female	4	9	4	9	1	3	2	3	47	24	106
Male	1	2	2	0	0	0	1	0	16	9	31
Ethnicity
Units: Subjects
Hispanic or Latino	2	2	0	0	0	0	0	0	10	7	21
Not Hispanic or Latino	3	9	6	9	1	3	3	3	53	26	116
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0	0
Race
Units: Subjects
American Indian or Alaskan Native	0	0	0	0	0	0	0	0	0	0	0
Asia	0	0	0	0	0	0	0	0	1	0	1
Native Hawaiian or Pacific Islander	0	0	0	0	0	0	0	0	0	0	0
Black or African American	0	1	0	0	0	3	0	0	14	5	23
White	5	10	5	9	1	0	3	3	47	28	111
More than one Race	0	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	1	0	0	0	0	0	1	0	2
6-Minute Walk Test (6MWT)[1]
[1] Measure Analysis Population Description: Modified Intent-to-treat (mITT) population, which included all randomized patients who received at least 28 doses of study treatment, did not undergo heart or lung transplantation during the treatment period, and performed at least one-post baseline 6MWT assessment. Only Part 1 patients are included since the primary outcome is the change from baseline in 6MWD through Week 16
Units: Meters
arithmetic mean (standard deviation)	±	±	±	±	±	±	±	±	±	±	±	±	±

End points

Top of page

Reporting group title

Part 1:Dose Ranging Bardoxolone Methyl 2.5mg

Reporting group description

Reporting group title

Part 1:Dose-Ranging Bardoxolone Methyl 5mg

Reporting group description

Reporting group title

Part 1:Dose-Ranging Bardoxolone Methyl 10mg

Reporting group description

Reporting group title

Part 1:Dose-Ranging Bardoxolone Methyl 20mg

Reporting group description

Reporting group title

Part 1:Dose-Ranging Placebo 2.5mg

Reporting group description

Reporting group title

Part 1: Dose-Ranging Placebo 5 mg

Reporting group description

Reporting group title

Part 1: Dose-Ranging Placebo 10 mg

Reporting group description

Reporting group title

Part 1: Dose-Ranging Placebo 20 mg

Reporting group description

Reporting group title

Part 1: Dose Titration: Bardoxolone Methyl 10 mg

Reporting group description

Reporting group title

Part 1: Dose Titration: Placebo 10 mg

Reporting group description

Reporting group title

Part 2: Open-Label Bardoxolone Methyl 2.5 mg

Reporting group description

Reporting group title

Part 2: Open-Label Bardoxolone Methyl 5 mg

Reporting group description

Reporting group title

Part 2: Open-Label Bardoxolone Methyl 10 mg

Reporting group description

Reporting group title

Part 2: Open-Label Bardoxolone Methyl 20 mg

Reporting group description

Reporting group title

Part 2: Bardoxolone Methyl 2.5 mg

Reporting group description

Reporting group title

Part 2: Bardoxolone Methyl 5 mg

Reporting group description

Reporting group title

Part 2: Bardoxolone Methyl 10 mg

Reporting group description

Reporting group title

Part 2: Bardoxolone Methyl 20 mg

Reporting group description

Reporting group title

Part 2: Bardoxolone Methyl 10 mg

Reporting group description

Reporting group title

Part 2: Bardoxolone methyl capsules 10mg

Reporting group description

Subject analysis set title

Part 2: Open-Label Bardoxolone Methyl 2.5 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 were eligible to continue to the extension Part 2 and continued to receive the same bardoxolone methyl 2.5 mg once-daily from Week 16 onwards.

Subject analysis set title

Part 2: Open-Label Bardoxolone Methyl 5mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 were eligible to continue to the extension Part 2 and continued to receive the same bardoxolone methyl 5 mg once-daily from Week 16 onwards.

Subject analysis set title

Part 2: Open-Label Bardoxolone Methyl 10 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 wer eligible to continue to the extension Part 2 and continued to receive the same bardoxolone methyl 10 mg once-daily from Week 16 onwards.

Subject analysis set title

Part 2: Open-Label Bardoxolone Methyl 20 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 were eligible to continue to the extension Part 2 and continued to receive the same bardoxolone methyl 20 mg once-daily from Week 16 onwards.

Subject analysis set title

Part 2: Bardoxolone Methyl 2.5 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 were eligible to continue to the extension Part 2 and received bardoxolone methyl 2.5 mg once-daily from Week 16 and onwards.

Subject analysis set title

Part 2: Bardoxolone Methyl 5 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 were eligible to continue to the extension Part 2 and received bardoxolone methyl 5 mg once-daily from Week 16 and onwards.

Subject analysis set title

Part 2: Bardoxolone Methyl 10 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 were eligible to continue to the extension Part 2 and received bardoxolone methyl 10 mg once-daily from Week 16 and onwards.

Subject analysis set title

Part 2: Bardoxolone Methyl 20 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 were eligible to continue to the extension Part 2 and received bardoxolone methyl 20 mg once-daily from Week 16 and onwards.

Subject analysis set title

Part 2: Bardoxolone Methyl 10 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Participants who completed treatment in Part 1 were eligible to continue to the extension Part 2 and received the same bardoxolone methyl dose once-daily from Week 16 and onwards.

Subject analysis set title

Part 2: Bardoxolone Methyl 10 mg

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Part 2: Total

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 2: Open-label extension period (Week 16 and onwards)

Subject analysis set title

Change from Baseline though Week 16 for participants with PH

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Change from Baseline though Week 16 for participants with PH

Subject analysis set type

Intention-to-treat

Subject analysis set description

Part 1: Dose Titration: Placebo 10 mg

Primary: Change From Baseline Though Week 16 in 6-Minute Walk Distance (6MWD) for Bardoxolone Methyl Compared to Placebo

Top of page

End point title

Change From Baseline Though Week 16 in 6-Minute Walk Distance (6MWD) for Bardoxolone Methyl Compared to Placebo

End point description

Overall treatment effect in exercise capacity, as measured by the total distance walked in 6 minutes (6MWD) mean change from baseline though Week 16. A lower 6MWD reflects greater severity thus, a positive change from baseline suggests an improvement.

End point type

Primary

End point timeframe

Baseline through Week 16

Part 1:Dose Ranging Bardoxolone Methyl 2.5mg

Part 1:Dose-Ranging Bardoxolone Methyl 5mg

Part 1:Dose-Ranging Bardoxolone Methyl 10mg

Part 1:Dose-Ranging Bardoxolone Methyl 20mg

Part 1:Dose-Ranging Placebo 2.5mg

Part 1: Dose-Ranging Placebo 5 mg

Part 1: Dose-Ranging Placebo 10 mg

Part 1: Dose-Ranging Placebo 20 mg

Part 1: Dose Titration: Bardoxolone Methyl 10 mg

Part 1: Dose Titration: Placebo 10 mg

Change from Baseline though Week 16 for participants with PH

Number of subjects analysed

41 ^[1]

21 ^[2]

Units: Meters

arithmetic mean (standard deviation)

32.5 ± 29.14

24 ± 30.08

3.4 ± 31.28

-3.2 ± 39.53

20.3 ± 13.08

24.6 ± 59.4

23.8 ± 34.54

-21.8 ± 4.17

13.9 ± 41.15

19.4 ± 21.06

7.6 ± 32.01

10.8 ± 32.01

Notes
[1] - Change from Baseline though Week 16 for participants with PH in the Part 1: Dose Titration Bard 10mg
[2] - Change from Baseline though Week 16 for participants w/PH in the Part 1 Dose Titration Placebo 10mg

Statistical Analysis 1

Statistical analysis description

Comparison Group Selection Part 1: Dose-Ranging Bardoxolone Methyl 2.5 mg/Part 2: Open-Label, Part 1: Dose-Ranging Bardoxolone Methyl 5 mg/Part 2: Open-Label, Part 1: Dose-Ranging Bardoxolone Methyl 10 mg/Part 2: Open-Label, Part 1: Dose-Ranging Bardoxolone Methyl 20 mg/Part 2: Open-Label, Part 1: Dose-Ranging Placebo 2.5 mg/Part 2: Bardoxolone Methyl 2.5 mg, Part 1: Dose-Ranging Placebo 5 mg/Part 2: Bardoxolone Methyl 5 mg, Part 1: Dose-Ranging Placebo 10 mg/Part 2: Bardoxolone Methyl 10 mg, Pa

Comparison groups

Part 1:Dose-Ranging Bardoxolone Methyl 10mg v Part 1:Dose-Ranging Bardoxolone Methyl 20mg v Part 1:Dose-Ranging Placebo 2.5mg v Part 1: Dose-Ranging Placebo 5 mg v Part 1: Dose-Ranging Placebo 10 mg v Part 1: Dose-Ranging Placebo 20 mg v Part 1: Dose Titration: Bardoxolone Methyl 10 mg v Part 1: Dose Titration: Placebo 10 mg v Part 1:Dose-Ranging Bardoxolone Methyl 5mg v Part 1:Dose Ranging Bardoxolone Methyl 2.5mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.8133 ^[4]

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-1.74

Confidence interval

level

95%

sides

2-sided

lower limit

-16.22

upper limit

12.74

Notes
[3] - Overall treatment effect in participants with PAH. Mean overall treatment effect across all visits for change from baseline in 6MWD was estimated and compared with placebo through 16 weeks of treatment using mixed-model repeated measures (MMRM), with treatment group, visit, and the interaction between treatment and visit as fixed factors. A compound symmetry covariance matrix was assumed. Data from Wks 4, 8, 12, and 16 used in the model with the change from baseline at Wk16 as primary endpoint.
[4] - The p-value comparison is for the difference in the change in 6WMD from baseline at Week 16 for bardoxolone methyl relative to placebo in participants with pulmonary arterial hypertension (PAH)

Statistical Analysis 2

Statistical analysis description

Part 1: Dose Titration: Bardoxolone Methyl 10 mg/Part 2: Bardoxolone Methyl 10 mg, Part 1: Dose Titration: Placebo 10 mg/Part 2: Bardoxolone Methyl 10 mg

Comparison groups

Part 1: Dose Titration: Bardoxolone Methyl 10 mg v Part 1: Dose Titration: Placebo 10 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

= 0.759 ^[6]

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-3.17

Confidence interval

level

95%

sides

2-sided

lower limit

-23.54

upper limit

17.2

Notes
[5] - Overall treatment effect in participants with PH. Mean overall treatment effect across all visits for change from baseline in 6MWD was estimated & compared with placebo through 16 wks of treatment using mixed-model repeated measures (MMRM), with treatment group, visit, and the interaction between treatment & visit as fixed factors. Compound symmetry covariance matrix was assumed. Data from Wks 4, 8, 12, and 16 were used in the model with the change from baseline at Wk 16 as the primary endpoint
[6] - The p-value comparison is for the difference in the change in 6WMD from baseline at Week 16 for bardoxolone methyl relative to placebo in participants with pulmonary hypertension (PH)

Adverse events

Top of page

Timeframe for reporting adverse events

Part 1: 16-week double-blind, randomized, placebo-controlled treatment period (Day 1 to Week 16). Part 2: Open-label extension period (Week 16 onwards). Part 2 is the extension period, patients were to stay until study drug became available through EAP.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Part 1 of Part 1: Dose-Ranging BM 5 mg/Part 2: Open-Label

Reporting group description

Part 1: Participants were randomized to receive bardoxolone methyl 5 mg once-daily from Day 1 to Week 16.

Reporting group title

Part 1 of Part 1: Dose-Ranging BM 2.5 mg/Part 2: Open-Label

Reporting group description

Part 1: Participants were randomized to receive bardoxolone methyl 2.5 mg once-daily from Day 1 to Week 16.

Reporting group title

Part 1 of Part 1: Dose-Ranging BM 10 mg/Part 2: Open-Label

Reporting group description

Part 1: Participants were randomized to receive bardoxolone methyl 10 mg once-daily from Day 1 to Week 16.

Reporting group title

Part 1 of Part 1: Dose-Ranging BM 20 mg/Part 2: Open-Label

Reporting group description

Part 1: Participants were randomized to receive bardoxolone methyl 20 mg once-daily from Day 1 to Week 16.

Reporting group title

Part 1 of Part 1: Dose-Ranging Pbo 2.5 mg/Part 2: BM 2.5 mg

Reporting group description

Part 1: Participants were randomized to receive bardoxolone methyl matching placebo 2.5 mg capsules once-daily from Day 1 to Week 16.

Reporting group title

Part 1 of Part 1: Dose-Ranging Pbo 5 mg/Part 2: BM 5 mg

Reporting group description

Part 1: Participants were randomized to receive bardoxolone methyl matching placebo 5 mg capsules once-daily from Day 1 to Week 16.

Reporting group title

Part 1 of Part 1: Dose-Ranging Pbo 10 mg/Part 2: BM 10 mg

Reporting group description

Part 1: Participants were randomized to receive bardoxolone methyl matching placebo 10 mg capsules once-daily from Day 1 to Week 16.

Reporting group title

Part 1 of Part 1: Dose Titration: BM 10 mg/Part 2: BM 10 mg

Reporting group description

Part 1: Participants were randomized to receive bardoxolone methyl 10 mg capsules. Participants initially started with bardoxolone methyl 5 mg once-daily from Day 1 and titrated to bardoxolone methyl 10 mg once-daily starting at Week 4 up to Week 16.

Reporting group title

Part 1 of Part 1: Dose-Ranging Pbo 20 mg/Part 2: BM 20 mg

Reporting group description

Part 1: Participants were randomized to receive bardoxolone methyl matching placebo 20 mg capsules once-daily from Day 1 to Week 16.

Reporting group title

Part 1 of Part 1: Dose Titration: Pbo 10 mg/Part 2: BM 10 mg

Reporting group description

Part 1: Participants were randomized to receive bardoxolone methyl matching placebo 10 mg capsules once-daily from Day 1 to Week 16.

Reporting group title

Part 2 of Part 1: Dose-Ranging BM 2.5 mg/Part 2: Open-Label

Reporting group description

Part 2: Participants who completed treatment receiving bardoxolone methyl 2.5 mg once daily in Part 1 were eligible to continue to the extension Part 2 and continued to receive the same bardoxolone methyl 2.5 mg once-daily from Week 16 onwards.

Reporting group title

Part 2 of Part 1: Dose-Ranging BM 5 mg/Part 2: Open-Label

Reporting group description

Part 2: Participants who completed treatment receiving bardoxolone methyl 5 mg once daily in Part 1 were eligible to continue to the extension Part 2 and continued to receive the same bardoxolone methyl 5 mg once-daily from Week 16 onwards.

Reporting group title

Part 2 of Part 1: Dose-Ranging BM 10 mg/Part 2: Open-Label

Reporting group description

Part 2: Participants who completed treatment receiving bardoxolone methyl 10 mg once daily in Part 1 were eligible to continue to the extension Part 2 and continued to receive the same bardoxolone methyl 10 mg once-daily from Week 16 onwards.

Reporting group title

Part 2 of Part 1: Dose-Ranging BM 20 mg/Part 2: Open-Label

Reporting group description

Part 2: Participants who completed treatment receiving bardoxolone methyl 20 mg once daily in Part 1 were eligible to continue to the extension Part 2 and continued to receive the same bardoxolone methyl 20 mg once-daily from Week 16 onwards.

Reporting group title

Part 2 of Part 1: Dose-Ranging Pbo 2.5 mg/Part 2: BM 2.5 mg

Reporting group description

Part 2: Participants who completed bardoxolone methyl matching placebo 2.5 mg capsules once-daily treatment in Part 1 were eligible to continue to the extension Part 2 and received bardoxolone methyl 2.5 mg once-daily from Week 16 and onwards.

Reporting group title

Part 2 of Part 1: Dose-Ranging Pbo 5 mg/Part 2: BM 5 mg

Reporting group description

Part 2: Participants who completed bardoxolone methyl matching placebo 5 mg capsules once-daily treatment in Part 1 were eligible to continue to the extension Part 2 and received bardoxolone methyl 5 mg once-daily from Week 16 and onwards.

Reporting group title

Part 2 of Part 1: Dose-Ranging Pbo 10 mg/Part 2: BM 10 mg

Reporting group description

Part 2: Participants who completed bardoxolone methyl matching placebo 10 mg capsules once-daily treatment in Part 1 were eligible to continue to the extension Part 2 and received bardoxolone methyl 10 mg once-daily from Week 16 and onwards.

Reporting group title

Part 2 of Part 1: Dose-Ranging Pbo 20 mg/Part 2: BM 20 mg

Reporting group description

Part 2: Participants who completed bardoxolone methyl matching placebo 20 mg capsules once-daily treatment in Part 1 were eligible to continue to the extension Part 2 and received bardoxolone methyl 20 mg once-daily from Week 16 and onwards.

Reporting group title

Part 2 of Part 1: Dose Titration: BM 10 mg/Part 2: BM 10 mg

Reporting group description

Part 2: Participants who completed treatment titrated to 10 mg bardoxolone methyl in Part 1 were eligible to continue to the extension Part 2 and received bardoxolone methyl 10 mg once-daily from Week 16 and onwards.

Reporting group title

Part 2 of Part 1: Dose Titration: Pbo 10 mg/Part 2: BM 10 mg

Reporting group description

Part 2: Participants who completed bardoxolone methyl matching placebo 10 mg capsules once-daily treatment in Part 1 were eligible to continue to the extension Part 2 and initially received bardoxolone methyl 5 mg once-daily from Week 16 thru Week 20 and bardoxolone methyl 10 mg from Week 20 and onwards.

Part 1 of Part 1: Dose-Ranging BM 5 mg/Part 2: Open-Label

Part 1 of Part 1: Dose-Ranging BM 2.5 mg/Part 2: Open-Label

Part 1 of Part 1: Dose-Ranging BM 10 mg/Part 2: Open-Label

Part 1 of Part 1: Dose-Ranging BM 20 mg/Part 2: Open-Label

Part 1 of Part 1: Dose-Ranging Pbo 2.5 mg/Part 2: BM 2.5 mg

Part 1 of Part 1: Dose-Ranging Pbo 5 mg/Part 2: BM 5 mg

Part 1 of Part 1: Dose-Ranging Pbo 10 mg/Part 2: BM 10 mg

Part 1 of Part 1: Dose Titration: BM 10 mg/Part 2: BM 10 mg

Part 1 of Part 1: Dose-Ranging Pbo 20 mg/Part 2: BM 20 mg

Part 1 of Part 1: Dose Titration: Pbo 10 mg/Part 2: BM 10 mg

Part 2 of Part 1: Dose-Ranging BM 2.5 mg/Part 2: Open-Label

Part 2 of Part 1: Dose-Ranging BM 5 mg/Part 2: Open-Label

Part 2 of Part 1: Dose-Ranging BM 10 mg/Part 2: Open-Label

Part 2 of Part 1: Dose-Ranging BM 20 mg/Part 2: Open-Label

Part 2 of Part 1: Dose-Ranging Pbo 2.5 mg/Part 2: BM 2.5 mg

Part 2 of Part 1: Dose-Ranging Pbo 5 mg/Part 2: BM 5 mg

Part 2 of Part 1: Dose-Ranging Pbo 10 mg/Part 2: BM 10 mg

Part 2 of Part 1: Dose-Ranging Pbo 20 mg/Part 2: BM 20 mg

Part 2 of Part 1: Dose Titration: BM 10 mg/Part 2: BM 10 mg

Part 2 of Part 1: Dose Titration: Pbo 10 mg/Part 2: BM 10 mg

Total subjects affected by serious adverse events

subjects affected / exposed

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 11 (0.00%)

2 / 12 (16.67%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

7 / 74 (9.46%)

1 / 4 (25.00%)

2 / 38 (5.26%)

2 / 5 (40.00%)

5 / 11 (45.45%)

3 / 6 (50.00%)

6 / 9 (66.67%)

0 / 1 (0.00%)

1 / 3 (33.33%)

2 / 3 (66.67%)

1 / 3 (33.33%)

9 / 63 (14.29%)

9 / 33 (27.27%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Basal cell carcinoma

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 74 (1.35%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Hypertensive crisis

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

1 / 6 (16.67%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (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 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

1 / 9 (11.11%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (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

Raynaud's phenomenon

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 63 (1.59%)

0 / 33 (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

General physical health deterioration

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Non-cardiac chest pain

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 74 (1.35%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (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

Reproductive system and breast disorders

Haemorrhagic ovarian cyst

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 63 (1.59%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hypoxia

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 74 (1.35%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

1 / 9 (11.11%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (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

Pleural effusion

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 74 (1.35%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pleuritic pain

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 63 (1.59%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary arterial hypertension

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

1 / 12 (8.33%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

1 / 9 (11.11%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 63 (1.59%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary fibrosis

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pulmonary hypertension

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

1 / 6 (16.67%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Delirium

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

International normalised ratio increased

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 63 (1.59%)

0 / 33 (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

Hip fracture

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

1 / 5 (20.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumothorax traumatic

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Subdural haematoma

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Wound

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 63 (1.59%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Acute right ventricular failure

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atrial fibrillation

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 74 (1.35%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac failure acute

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 63 (1.59%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac tamponade

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 63 (1.59%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Coronary artery disease

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pericardial effusion

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Right ventricular failure

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 63 (1.59%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ventricular arrhythmia

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 74 (1.35%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (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

Nervous system disorders

Dizziness

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

1 / 6 (16.67%)

0 / 9 (0.00%)

0 / 1 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (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

Embolic stroke

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

1 / 5 (20.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Syncope

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

1 / 9 (11.11%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (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

Transient ischaemic attack

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

1 / 9 (11.11%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (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

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

1 / 9 (11.11%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (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

Ascites

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastric ulcer

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal haemorrhage

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

1 / 9 (11.11%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (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 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 63 (1.59%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Nephrolithiasis

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Renal failure acute

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Back pain

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 63 (1.59%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Muscular weakness

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

1 / 4 (25.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Osteoarthritis

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

1 / 5 (20.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (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 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

1 / 4 (25.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 63 (0.00%)

0 / 33 (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

Systemic lupus erythematosus

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Bronchitis

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Campylobacter gastroenteritis

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Cellulitis

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 74 (1.35%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

1 / 6 (16.67%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (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

Diarrhoea infectious

subjects affected / exposed

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Escherichia urinary tract infection

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 63 (1.59%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Influenza

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

1 / 38 (2.63%)

0 / 5 (0.00%)

0 / 11 (0.00%)

1 / 6 (16.67%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (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

Lung infection

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

1 / 38 (2.63%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (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 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

1 / 12 (8.33%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

1 / 38 (2.63%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

1 / 9 (11.11%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 63 (1.59%)

1 / 33 (3.03%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Salpingitis

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 63 (1.59%)

0 / 33 (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 enterococcal

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 63 (1.59%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urosepsis

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

1 / 9 (11.11%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Viral upper respiratory tract infection

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

1 / 9 (11.11%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Dehydration

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

0 / 4 (0.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 63 (0.00%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Fluid overload

subjects affected / exposed

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 12 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 74 (0.00%)

1 / 4 (25.00%)

0 / 38 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 9 (0.00%)

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 63 (1.59%)

0 / 33 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Part 1 of Part 1: Dose-Ranging BM 5 mg/Part 2: Open-Label	Part 1 of Part 1: Dose-Ranging BM 2.5 mg/Part 2: Open-Label	Part 1 of Part 1: Dose-Ranging BM 10 mg/Part 2: Open-Label	Part 1 of Part 1: Dose-Ranging BM 20 mg/Part 2: Open-Label	Part 1 of Part 1: Dose-Ranging Pbo 2.5 mg/Part 2: BM 2.5 mg	Part 1 of Part 1: Dose-Ranging Pbo 5 mg/Part 2: BM 5 mg	Part 1 of Part 1: Dose-Ranging Pbo 10 mg/Part 2: BM 10 mg	Part 1 of Part 1: Dose Titration: BM 10 mg/Part 2: BM 10 mg	Part 1 of Part 1: Dose-Ranging Pbo 20 mg/Part 2: BM 20 mg	Part 1 of Part 1: Dose Titration: Pbo 10 mg/Part 2: BM 10 mg	Part 2 of Part 1: Dose-Ranging BM 2.5 mg/Part 2: Open-Label	Part 2 of Part 1: Dose-Ranging BM 5 mg/Part 2: Open-Label	Part 2 of Part 1: Dose-Ranging BM 10 mg/Part 2: Open-Label	Part 2 of Part 1: Dose-Ranging BM 20 mg/Part 2: Open-Label	Part 2 of Part 1: Dose-Ranging Pbo 2.5 mg/Part 2: BM 2.5 mg	Part 2 of Part 1: Dose-Ranging Pbo 5 mg/Part 2: BM 5 mg	Part 2 of Part 1: Dose-Ranging Pbo 10 mg/Part 2: BM 10 mg	Part 2 of Part 1: Dose-Ranging Pbo 20 mg/Part 2: BM 20 mg	Part 2 of Part 1: Dose Titration: BM 10 mg/Part 2: BM 10 mg	Part 2 of Part 1: Dose Titration: Pbo 10 mg/Part 2: BM 10 mg
Total subjects affected by non serious adverse events
subjects affected / exposed	11 / 12 (91.67%)	5 / 6 (83.33%)	10 / 11 (90.91%)	12 / 12 (100.00%)	2 / 2 (100.00%)	4 / 4 (100.00%)	3 / 3 (100.00%)	63 / 74 (85.14%)	4 / 4 (100.00%)	33 / 38 (86.84%)	5 / 5 (100.00%)	11 / 11 (100.00%)	6 / 6 (100.00%)	8 / 9 (88.89%)	1 / 1 (100.00%)	2 / 3 (66.67%)	3 / 3 (100.00%)	3 / 3 (100.00%)	47 / 63 (74.60%)	30 / 33 (90.91%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Colon cancer
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Squamous cell carcinoma
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Squamous cell carcinoma of skin
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Uterine leiomyoma
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0
Vascular disorders
Flushing
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	2 / 12 (16.67%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	0	2	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Hot flush
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	2
Hypertension
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	1	0	0	0	0	2	0	0	0	0	1	0	0	0	0	0	0	1
Hypotension
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	2 / 38 (5.26%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	1	0	0	0	0	0	2	0	0	1	0	0	0	1	0	0	1
Orthostatic hypotension
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Thrombophlebitis superficial
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	1 / 4 (25.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	1
Chest discomfort
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1
Chills
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Fatigue
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 11 (9.09%)	2 / 12 (16.67%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	7 / 74 (9.46%)	0 / 4 (0.00%)	4 / 38 (10.53%)	0 / 5 (0.00%)	0 / 11 (0.00%)	3 / 6 (50.00%)	1 / 9 (11.11%)	1 / 1 (100.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	4 / 63 (6.35%)	4 / 33 (12.12%)
occurrences all number	1	0	1	2	0	0	1	7	0	4	0	0	3	1	1	1	1	0	4	4
Generalised oedema
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0
Implant site haematoma
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Irritability
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Malaise
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Non-cardiac chest pain
subjects affected / exposed	0 / 12 (0.00%)	1 / 6 (16.67%)	1 / 11 (9.09%)	1 / 12 (8.33%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	3 / 74 (4.05%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	4 / 63 (6.35%)	0 / 33 (0.00%)
occurrences all number	0	1	1	1	0	1	0	3	0	0	0	0	0	1	0	1	1	0	4	0
Oedema
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Oedema peripheral
subjects affected / exposed	3 / 12 (25.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	3 / 74 (4.05%)	0 / 4 (0.00%)	5 / 38 (13.16%)	2 / 5 (40.00%)	3 / 11 (27.27%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	4 / 63 (6.35%)	3 / 33 (9.09%)
occurrences all number	3	0	1	0	0	0	1	3	0	5	2	3	1	0	0	0	0	0	4	3
Pain
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	2 / 12 (16.67%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	2 / 33 (6.06%)
occurrences all number	1	0	0	2	0	0	0	1	0	1	0	0	0	1	0	0	0	0	0	2
Pyrexia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	2 / 38 (5.26%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	2	0	2	0	0	1	0	0	0	0	0	0	2
Vessel puncture site haematoma
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Vessel puncture site pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vessel puncture site swelling
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1
Seasonal allergy
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Social circumstances
Menopause
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Breast mass
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1
Dysmenorrhoea
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Menorrhagia
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Menstrual disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 63 (0.00%)	0 / 33 (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
Menstruation irregular
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Ovarian cyst
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Vaginal disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Vaginal haemorrhage
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	0	1	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Bronchial hyperreactivity
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Cough
subjects affected / exposed	1 / 12 (8.33%)	1 / 6 (16.67%)	2 / 11 (18.18%)	1 / 12 (8.33%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	4 / 74 (5.41%)	0 / 4 (0.00%)	4 / 38 (10.53%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	5 / 63 (7.94%)	4 / 33 (12.12%)
occurrences all number	1	1	2	1	0	1	0	4	0	4	0	1	0	0	0	0	1	0	5	4
Dyspnoea
subjects affected / exposed	2 / 12 (16.67%)	1 / 6 (16.67%)	3 / 11 (27.27%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	8 / 74 (10.81%)	0 / 4 (0.00%)	1 / 38 (2.63%)	1 / 5 (20.00%)	2 / 11 (18.18%)	1 / 6 (16.67%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	5 / 63 (7.94%)	4 / 33 (12.12%)
occurrences all number	2	1	3	0	0	0	0	8	0	1	1	2	1	1	0	0	1	0	5	4
Dyspnoea exertional
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	0	1	0	0	0	2	0	1	0	1	0	0	0	0	0	0	0	0
Dyspnoea paroxysmal nocturnal
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Epistaxis
subjects affected / exposed	1 / 12 (8.33%)	1 / 6 (16.67%)	1 / 11 (9.09%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	2 / 38 (5.26%)	1 / 5 (20.00%)	0 / 11 (0.00%)	4 / 6 (66.67%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 63 (1.59%)	1 / 33 (3.03%)
occurrences all number	1	1	1	1	0	0	0	2	0	2	1	0	4	1	0	0	1	0	1	1
Hypoxia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1
Increased upper airway secretion
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Mediastinal mass
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Nasal congestion
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	3 / 33 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	1	0	0	0	0	0	3
Nasal dryness
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Nasal septum perforation
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1
Oropharyngeal pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	2 / 4 (50.00%)	0 / 3 (0.00%)	3 / 74 (4.05%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	1 / 11 (9.09%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 63 (1.59%)	2 / 33 (6.06%)
occurrences all number	0	0	0	1	0	2	0	3	0	1	0	1	1	0	0	0	1	0	1	2
Pharyngeal lesion
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Pleural effusion
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0
Productive cough
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 63 (4.76%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	1
Pulmonary arterial hypertension
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0
Pulmonary congestion
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	1	0	1	1	0	0	0	0	0	0
Pulmonary fibrosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Pulmonary hypertension
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Rales
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	1	1
Rhinalgia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Rhinorrhoea
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Sinus congestion
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	3 / 38 (7.89%)	1 / 5 (20.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	1	0	2	0	3	1	0	1	0	0	0	0	0	1	0
Sleep apnoea syndrome
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	1
Upper-airway cough syndrome
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1
Wheezing
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Psychiatric disorders
Anxiety
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	1 / 33 (3.03%)
occurrences all number	1	0	0	1	0	0	0	2	0	0	0	0	0	0	0	0	0	0	1	1
Attention deficit/hyperactivity disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Confusional state
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Depression
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	1
Hallucination
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Insomnia
subjects affected / exposed	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	1 / 38 (2.63%)	1 / 5 (20.00%)	1 / 11 (9.09%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	1	0	1	0	0	0	1	0	1	1	1	1	0	0	0	0	0	1	0
Libido decreased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	5 / 74 (6.76%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 63 (1.59%)	2 / 33 (6.06%)
occurrences all number	0	0	0	1	0	0	0	5	0	0	0	0	1	0	1	0	1	0	1	2
Aspartate aminotransferase increased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	4 / 74 (5.41%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	1 / 33 (3.03%)
occurrences all number	0	0	0	1	0	0	0	4	0	0	0	0	1	0	1	0	0	0	1	1
Blood bicarbonate decreased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Blood bilirubin increased
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Blood creatinine increased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 63 (3.17%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Blood phosphorus decreased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Blood potassium decreased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood urine present
subjects affected / exposed	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Brain natriuretic peptide increased
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	3 / 74 (4.05%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 63 (4.76%)	3 / 33 (9.09%)
occurrences all number	1	0	0	0	0	0	0	3	0	1	0	0	0	0	0	0	0	0	3	3
Cardiac murmur
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Cardiac output increased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Electrocardiogram abnormal
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	3 / 74 (4.05%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0	0	0	0	0	0	0	0	1	0	0	0
Heart rate increased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0
Hepatic enzyme increased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1
International normalised ratio increased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0
Liver function test abnormal
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	2 / 33 (6.06%)
occurrences all number	1	0	0	1	0	0	0	2	0	1	0	0	0	0	0	0	0	0	1	2
N-terminal prohormone brain natriuretic peptide increased
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	2 / 38 (5.26%)	1 / 5 (20.00%)	2 / 11 (18.18%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	4 / 63 (6.35%)	2 / 33 (6.06%)
occurrences all number	1	0	0	0	0	0	0	2	0	2	1	2	0	0	0	0	0	0	4	2
Oxygen saturation decreased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	1 / 11 (9.09%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	1	0	0	0	0	0	0	0
Platelet count decreased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0
Pulmonary arterial pressure increased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Serum ferritin decreased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	1	0
Venous pressure jugular increased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 63 (3.17%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	2	0
Vital capacity abnormal
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Weight decreased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	2 / 12 (16.67%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	3 / 74 (4.05%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	1 / 11 (9.09%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 63 (1.59%)	2 / 33 (6.06%)
occurrences all number	0	0	0	2	0	0	1	3	0	1	0	1	1	0	0	0	1	0	1	2
Weight increased
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	2 / 4 (50.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	2	1	0	0	0	0	0	0	0	0	0	0
White blood cell count increased
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 63 (4.76%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	3 / 74 (4.05%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	1	0	1	3	0	0	0	0	1	0	0	0	0	0	1	1
Foot fracture
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Hip fracture
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Joint dislocation
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Joint injury
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Laceration
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 63 (4.76%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	3	0
Ligament sprain
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 63 (3.17%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	2	0
Limb injury
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1
Muscle injury
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Procedural pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	1	0	0	1	0	0	1	0	0	0
Radius fracture
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Rib fracture
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0
Upper limb fracture
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Wound haemorrhage
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Congenital, familial and genetic disorders
Arteriovenous malformation
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Cardiac disorders
Angina pectoris
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Atrial fibrillation
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	1	0
Atrial flutter
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Cardiac discomfort
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Palpitations
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	2 / 12 (16.67%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	1 / 1 (100.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	2	0	0	0	2	0	0	1	1	0	0	1	1	0	0	0	1
Pericardial effusion
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 63 (3.17%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	2	0
Pericarditis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Postural orthostatic tachycardia syndrome
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Right ventricular failure
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Supraventricular extrasystoles
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Tachycardia
subjects affected / exposed	2 / 12 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	2	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0
Nervous system disorders
Ageusia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Burning sensation
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Central nervous system lesion
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Dizziness
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 11 (9.09%)	2 / 12 (16.67%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	4 / 74 (5.41%)	1 / 4 (25.00%)	3 / 38 (7.89%)	1 / 5 (20.00%)	1 / 11 (9.09%)	1 / 6 (16.67%)	1 / 9 (11.11%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	1	2	0	0	0	4	1	3	1	1	1	1	1	0	0	0	0	0
Dizziness exertional
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Dysgeusia
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	0	0	0	0	0	2	0	1	0	0	0	0	0	0	0	0	0	0
Headache
subjects affected / exposed	2 / 12 (16.67%)	0 / 6 (0.00%)	3 / 11 (27.27%)	5 / 12 (41.67%)	1 / 2 (50.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	8 / 74 (10.81%)	1 / 4 (25.00%)	7 / 38 (18.42%)	3 / 5 (60.00%)	0 / 11 (0.00%)	2 / 6 (33.33%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	2 / 63 (3.17%)	3 / 33 (9.09%)
occurrences all number	2	0	3	5	1	1	1	8	1	7	3	0	2	1	0	0	2	0	2	3
Memory impairment
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Migraine
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Multiple sclerosis
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Occipital neuralgia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Paraesthesia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1
Presyncope
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0
Sciatica
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	1	0
Somnolence
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	2 / 12 (16.67%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	1 / 4 (25.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	2	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Spinal claudication
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	1 / 4 (25.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Syncope
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	2 / 4 (50.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	2 / 38 (5.26%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	1	0	2	0	1	0	2	0	0	0	0	0	0	0	0	0	1
Tremor
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 12 (8.33%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 63 (4.76%)	0 / 33 (0.00%)
occurrences all number	1	1	0	0	0	0	0	1	0	0	1	1	0	1	0	0	0	0	3	0
Coagulopathy
subjects affected / exposed	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Iron deficiency anaemia
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	1 / 9 (11.11%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	1	1	0	1	0	0	1	0
Pancytopenia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Splenic vein thrombosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Splenomegaly
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Thrombocytopenia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	1
Ear and labyrinth disorders
Deafness
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Deafness bilateral
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Meniere's disease
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Tympanic membrane perforation
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Vertigo
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Eye disorders
Cataract
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	1	1	0	0	0	0	1	0
Conjunctival hyperaemia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Keratitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Ocular hyperaemia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Periorbital oedema
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Retinal tear
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Scleral disorder
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Vision blurred
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	1 / 33 (3.03%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1	0	0	0	0	1	1
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1
Abdominal distension
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 74 (1.35%)	1 / 4 (25.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	1	0	2	0	0	0	1	1	1	1	0	1	0	0	0	0	0	0	0	1
Abdominal pain
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 11 (9.09%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	4 / 74 (5.41%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	3 / 11 (27.27%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 63 (4.76%)	2 / 33 (6.06%)
occurrences all number	1	0	1	1	0	0	0	4	0	0	0	3	0	1	0	0	0	0	3	2
Abdominal pain lower
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Colonic polyp
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1
Constipation
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	3 / 74 (4.05%)	0 / 4 (0.00%)	3 / 38 (7.89%)	1 / 5 (20.00%)	3 / 11 (27.27%)	0 / 6 (0.00%)	2 / 9 (22.22%)	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	4 / 63 (6.35%)	1 / 33 (3.03%)
occurrences all number	1	0	0	1	0	1	0	3	0	3	1	3	0	2	0	1	1	0	4	1
Dental caries
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Diarrhoea
subjects affected / exposed	2 / 12 (16.67%)	0 / 6 (0.00%)	2 / 11 (18.18%)	2 / 12 (16.67%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	10 / 74 (13.51%)	0 / 4 (0.00%)	3 / 38 (7.89%)	2 / 5 (40.00%)	2 / 11 (18.18%)	0 / 6 (0.00%)	1 / 9 (11.11%)	1 / 1 (100.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 63 (1.59%)	7 / 33 (21.21%)
occurrences all number	2	0	2	2	0	1	0	10	0	3	2	2	0	1	1	0	1	0	1	7
Diverticulum
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Dry mouth
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	1	0	0	0	0	0	0	0	0	1	0
Duodenitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Dyspepsia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	1	0	0
Flatulence
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0	0	1	0	0	0	0	0	0
Frequent bowel movements
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Gastritis
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	2 / 12 (16.67%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	5 / 74 (6.76%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	2 / 33 (6.06%)
occurrences all number	0	1	0	2	0	0	0	5	0	0	0	0	0	1	0	0	0	0	1	2
Gingivitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Haematochezia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	2 / 38 (5.26%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Haemorrhoids
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	1
Hiatus hernia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Ileus
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Impaired gastric emptying
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Lip dry
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Lower gastrointestinal haemorrhage
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Nausea
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 11 (9.09%)	4 / 12 (33.33%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	10 / 74 (13.51%)	0 / 4 (0.00%)	6 / 38 (15.79%)	3 / 5 (60.00%)	4 / 11 (36.36%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	2 / 63 (3.17%)	3 / 33 (9.09%)
occurrences all number	1	0	1	4	0	1	0	10	0	6	3	4	0	1	0	0	1	1	2	3
Oesophageal spasm
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Painful defaecation
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Rectal haemorrhage
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Retching
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Salivary gland enlargement
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Toothache
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	1	0
Vomiting
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 11 (9.09%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	1 / 38 (2.63%)	2 / 5 (40.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 9 (22.22%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 63 (1.59%)	1 / 33 (3.03%)
occurrences all number	1	0	1	1	0	0	0	2	0	1	2	0	0	2	0	0	1	0	1	1
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Gallbladder disorder
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Gallbladder polyp
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hepatic cirrhosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Hepatic cyst
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	2 / 12 (16.67%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	2	0	1	0	0	0	0	1	0	0	1	0	0	1	0	0	0	0	0	0
Dermal cyst
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Digital ulcer
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Dry skin
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0
Erythema
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0
Hyperhidrosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Hyperkeratosis
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Increased tendency to bruise
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Pruritus
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	1	0	0	0	0	0	0	0	0	0	0
Psoriasis
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Rash
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Rash generalised
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 63 (0.00%)	0 / 33 (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
Rash papular
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	2 / 38 (5.26%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	2	0	0	0	0	0	0	0	0	1	0
Rash pruritic
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Skin haemorrhage
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Skin irritation
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Skin lesion
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0
Skin ulcer
subjects affected / exposed	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0
Subcutaneous nodule
subjects affected / exposed	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Urticaria
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Renal and urinary disorders
Cystitis noninfective
subjects affected / exposed	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Dysuria
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Pollakiuria
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Renal failure acute
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Urinary retention
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 12 (8.33%)	1 / 6 (16.67%)	1 / 11 (9.09%)	1 / 12 (8.33%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	3 / 74 (4.05%)	0 / 4 (0.00%)	1 / 38 (2.63%)	2 / 5 (40.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	4 / 63 (6.35%)	0 / 33 (0.00%)
occurrences all number	1	1	1	1	0	1	0	3	0	1	2	0	0	1	0	0	2	0	4	0
Arthritis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1
Arthropathy
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Back pain
subjects affected / exposed	3 / 12 (25.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	2 / 12 (16.67%)	1 / 2 (50.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	4 / 74 (5.41%)	0 / 4 (0.00%)	4 / 38 (10.53%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	1 / 33 (3.03%)
occurrences all number	3	0	0	2	1	1	0	4	0	4	0	1	0	0	0	0	0	0	1	1
Bone pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Bursitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Chondrocalcinosis pyrophosphate
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Clubbing
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Exostosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Fibromyalgia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Foot deformity
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Intervertebral disc degeneration
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	1 / 4 (25.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0
Intervertebral disc protrusion
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Joint swelling
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Muscle spasms
subjects affected / exposed	0 / 12 (0.00%)	1 / 6 (16.67%)	3 / 11 (27.27%)	3 / 12 (25.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	11 / 74 (14.86%)	0 / 4 (0.00%)	2 / 38 (5.26%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	5 / 63 (7.94%)	5 / 33 (15.15%)
occurrences all number	0	1	3	3	0	0	1	11	0	2	0	1	0	1	0	0	2	0	5	5
Musculoskeletal chest pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Musculoskeletal discomfort
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Musculoskeletal pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1
Myalgia
subjects affected / exposed	2 / 12 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 74 (1.35%)	0 / 4 (0.00%)	1 / 38 (2.63%)	2 / 5 (40.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	2	0	0	1	0	0	1	1	0	1	2	0	0	0	0	0	1	0	0	0
Neck pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	1 / 4 (25.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	1	0	0	0	0	0	0	0	0	0	1	0
Pain in extremity
subjects affected / exposed	2 / 12 (16.67%)	0 / 6 (0.00%)	1 / 11 (9.09%)	3 / 12 (25.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	2 / 74 (2.70%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 63 (4.76%)	1 / 33 (3.03%)
occurrences all number	2	0	1	3	0	0	1	2	0	0	0	0	0	0	0	2	0	0	3	1
Pain in jaw
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	2 / 5 (40.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0	1	0	0	0	0	0	0
Plantar fasciitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0
Rheumatoid arthritis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Scleroderma
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Temporomandibular joint syndrome
subjects affected / exposed	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Infections and infestations
Acute sinusitis
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Breast abscess
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Bronchitis
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	1 / 38 (2.63%)	2 / 5 (40.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	2 / 9 (22.22%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	1	0	0	1	0	0	0	2	0	1	2	1	0	2	0	0	1	0	1	0
Candidiasis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Cellulitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 63 (3.17%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	2	0
Clostridial infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1
Conjunctivitis bacterial
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Conjunctivitis infective
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 63 (0.00%)	0 / 33 (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
Ear infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	2 / 6 (33.33%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	2 / 33 (6.06%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	2
Folliculitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Gastroenteritis
subjects affected / exposed	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	1 / 38 (2.63%)	1 / 5 (20.00%)	2 / 11 (18.18%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	1	0	0	0	0	0	2	0	1	1	2	0	0	0	0	0	1	0	1
Gastrointestinal infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1
Helicobacter gastritis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Helicobacter infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Herpes zoster
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	1 / 33 (3.03%)
occurrences all number	0	0	0	1	0	0	0	2	0	0	0	0	0	1	0	0	0	0	1	1
Hordeolum
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Infected cyst
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Influenza
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	1
Laryngitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 63 (0.00%)	0 / 33 (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
Lower respiratory tract infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Lung infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Nasopharyngitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	2 / 3 (66.67%)	7 / 74 (9.46%)	0 / 4 (0.00%)	3 / 38 (7.89%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 63 (1.59%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	1	2	7	0	3	0	0	0	1	0	0	1	1	1	2
Oesophageal candidiasis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Oral herpes
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 63 (0.00%)	0 / 33 (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
Otitis externa
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Otitis media
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Pharyngitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 63 (3.17%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	1
Pneumonia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	2 / 11 (18.18%)	0 / 6 (0.00%)	2 / 9 (22.22%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	2	0	2	0	0	0	0	1	1
Pyelonephritis acute
subjects affected / exposed	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Respiratory tract infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	2 / 33 (6.06%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	2
Rhinitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	1	0
Sinusitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	4 / 74 (5.41%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	1 / 11 (9.09%)	1 / 6 (16.67%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	4 / 63 (6.35%)	2 / 33 (6.06%)
occurrences all number	0	0	0	1	0	0	0	4	0	0	1	1	1	1	0	0	0	0	4	2
Tooth abscess
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 74 (2.70%)	1 / 4 (25.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	2	1	1	0	1	0	0	0	0	0	0	1	1
Upper respiratory tract infection
subjects affected / exposed	2 / 12 (16.67%)	2 / 6 (33.33%)	2 / 11 (18.18%)	1 / 12 (8.33%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	10 / 74 (13.51%)	0 / 4 (0.00%)	7 / 38 (18.42%)	2 / 5 (40.00%)	4 / 11 (36.36%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	12 / 63 (19.05%)	9 / 33 (27.27%)
occurrences all number	2	2	2	1	0	0	0	10	0	7	2	4	0	1	0	0	1	1	12	9
Urinary tract infection
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 11 (9.09%)	3 / 12 (25.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	5 / 74 (6.76%)	1 / 4 (25.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	4 / 63 (6.35%)	2 / 33 (6.06%)
occurrences all number	1	0	1	3	0	0	0	5	1	1	0	0	1	1	0	0	0	2	4	2
Urinary tract infection bacterial
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Viral infection
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0
Vulvovaginal mycotic infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 12 (0.00%)	1 / 6 (16.67%)	3 / 11 (27.27%)	5 / 12 (41.67%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	7 / 74 (9.46%)	0 / 4 (0.00%)	1 / 38 (2.63%)	1 / 5 (20.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 63 (4.76%)	6 / 33 (18.18%)
occurrences all number	0	1	3	5	1	0	0	7	0	1	1	1	0	0	0	1	0	0	3	6
Dyslipidaemia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Fluid overload
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	1 / 4 (25.00%)	2 / 38 (5.26%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 9 (22.22%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 63 (4.76%)	0 / 33 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	1	2	0	0	0	2	0	0	0	0	3	0
Fluid retention
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	1 / 4 (25.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	1	0	0	0	0	1	1	1	0	0	0	1	0	0	0	0	0	1
Folate deficiency
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Glucose tolerance impaired
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 74 (1.35%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0
Gout
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0
Hyperalbuminaemia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Hypercholesterolaemia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	1 / 33 (3.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1
Hypokalaemia
subjects affected / exposed	2 / 12 (16.67%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	2 / 5 (40.00%)	2 / 11 (18.18%)	0 / 6 (0.00%)	2 / 9 (22.22%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 63 (1.59%)	1 / 33 (3.03%)
occurrences all number	2	1	0	0	0	0	0	0	0	0	2	2	0	2	0	0	1	0	1	1
Hypomagnesaemia
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 63 (1.59%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0
Iron deficiency
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	2 / 33 (6.06%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	1	0	0	0	0	0	2
Lactic acidosis
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 9 (11.11%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Lactose intolerance
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (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
Metabolic acidosis
subjects affected / exposed	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	0 / 38 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Vitamin B12 deficiency
subjects affected / exposed	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 12 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 74 (0.00%)	0 / 4 (0.00%)	1 / 38 (2.63%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 9 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 63 (0.00%)	0 / 33 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0

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Were there any global substantial amendments to the protocol? Yes

29 Oct 2013

Protocol Version 1.0 (No patients were enrolled under protocol version 1.0)

05 Dec 2013

Protocol Version 2.0

20 Aug 2014

Protocol Version 3.0

24 Nov 2014

Protocol Version 4.0

31 Aug 2015

Protocol Version 5.0

01 Jun 2016

Protocol Version 6.0

26 Jan 2017

Protocol Version 7.0

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 Dose-Ranging Study of the Efficacy and Safety of Bardoxolone Methyl in Patients with Pulmonary Hypertension (PH) - LARIAT

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Subject disposition

Baseline characteristics

Baseline characteristics

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End points

Primary: Change From Baseline Though Week 16 in 6-Minute Walk Distance (6MWD) for Bardoxolone Methyl Compared to Placebo

Primary: Change From Baseline Though Week 16 in 6-Minute Walk Distance (6MWD) for Bardoxolone Methyl Compared to Placebo

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Clinical trials

Clinical Trial Results: A Dose-Ranging Study of the Efficacy and Safety of Bardoxolone Methyl in Patients with Pulmonary Hypertension (PH) - LARIAT

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Baseline Though Week 16 in 6-Minute Walk Distance (6MWD) for Bardoxolone Methyl Compared to Placebo

Primary: Change From Baseline Though Week 16 in 6-Minute Walk Distance (6MWD) for Bardoxolone Methyl Compared to Placebo

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Dose-Ranging Study of the Efficacy and Safety of Bardoxolone Methyl in Patients with Pulmonary Hypertension (PH) - LARIAT