Clinical Trial Results:
Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of GBR 830 in Adult Subjects with Moderate to Severe Atopic Dermatitis. Eligible subjects participated in a 54-week treatment period, which comprised a randomised, placebo-controlled treatment period with ISB 830 (also known as GBR 830) for 16 weeks, followed by an open-label treatment period for 38 weeks. In the double-blind period, subjects were randomised 1:1:1:1:1:1 into 1 of 6 different dose groups: 4 dose groups in Part 1 (3 ISB 830; 1 placebo), and 2 dose groups in Part 2 (1 ISB 830; 1 placebo). Parts 1 and 2 of the study ran concurrently. All subjects in Groups 1 through 4 received a loading dose consisting of 2 subcutaneous (SC) injections, followed by 7 maintenance doses consisting of 1 SC injection per dose. For Groups 5 and 6, all subjects received a loading dose consisting of 4 SC injections, followed by 7 maintenance doses consisting of 2 SC injections per dose. The open-label treatment period comprised a 38-week treatment period during which each subject received an SC injection q2w from Week 16 to Week 52, or until subject withdrawal. All subjects who had been randomised to Groups 1-4 received 300 mg q2w, and subjects randomised to Groups 5-6 received 600 mg q2w. The primary objective was to evaluate the efficacy of ISB 830 monotherapy in adults with moderate to severe atopic dermatitis (AD) compared with placebo, as measured by percentage change from baseline in eczema area and severity index (EASI) score at Week 16.

Trial information Top of page
Trial identification
Sponsor protocol code	GBR830-204
Additional study identifiers
ISRCTN number	-
US NCT number	NCT03568162
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Ichnos Sciences SA
Sponsor organisation address	Rte de la Corniche 5A, Epalinges, Switzerland, 1066
Public contact	Regulatory Services, TMC Pharma Services Ltd, +44 1252842255, regulatory.services@tmcpharma.com
Scientific contact	Regulatory Services, TMC Pharma Services Ltd, +44 1252842255, regulatory.services@tmcpharma.com
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	22 Oct 2021
Is this the analysis of the primary completion data?	Yes
Primary completion date	03 Aug 2021
Global end of trial reached?	Yes
Global end of trial date	03 Aug 2021
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To characterise the efficacy of ISB 830 monotherapy in adults with moderate-to-severe AD compared with placebo as measured by percentage change from baseline in EASI score at Week 16.
Protection of trial subjects	The study protocol and all study related documents were reviewed and approved by the institutional ethics committee (IEC) or institutional review board (IRB) at each Investigator site before starting the study. This study was designed, conducted, and monitored in accordance with Sponsor procedures, which complied with the ethical principles of GCP as required by the major regulatory authorities, and in accordance with the Declaration of Helsinki. Subjects were to be removed from the study if any of the following circumstances occurred: 1. Withdrawal of consent by the subject. 2. Development of a serious or intolerable adverse event (AE) that necessitated discontinuation. 3. Severe laboratory abnormalities. 4. At the discretion of the Investigator, when he/she believed continued participation was not in the best interest of the subject. 5. At the discretion of the Investigator, when the subject did not adhere to the study procedures. 6. A positive pregnancy test. 7. A female partner of a male study subject became pregnant. 8. A protocol deviation that, in the opinion of the Sponsor and Investigator, warranted discontinuation from the study
Background therapy	The following medications and therapies not permitted during the study: • Investigational biological agent • Investigational drugs eg, phosphodiesterase type 4 (PDE4) inhibitors, Janus kinase inhibitors (JAK inhibitors) • Phototherapy for AD • Marketed drugs, including systemic corticosteroids, immunosuppressive/immunomodulatory drugs including, but not limited to cyclosporine, mycophenolate mofetil, IFN-γ, PDE4 inhibitors, JAK inhibitors, azathioprine, methotrexate • Topical medications including crisaborole, corticosteroids, tacrolimus, and/or pimecrolimus • Regular use (>2 visits/week) of a tanning booth/parlor • Cell-depleting agents including but not limited to rituximab • Infliximab, adalimumab, golimumab, certolizumab pegol, abatacept, etanercept, anakinra, dupilumab • Other biologics (not listed above) • Live (attenuated) vaccines All restrictions on the medications listed above were applicable for the entire duration of the study. Other concomitant medications that the subject received on a regular basis were continued, if in the opinion of the Investigator, they did not put the subject at undue risk or did not interfere with the study evaluations. Subjects who received rescue treatment with systemic corticosteroids, non-steroidal systemic immunosuppressive drugs, or biologics were discontinued temporarily. Administration of ISB 830 was to resume after the appropriate washout period (4 weeks or 5 half-lives, whichever was longer) and following discussion and upon obtaining written approval from the Sponsor’s medical monitor.
Evidence for comparator	There was no active comparator; all patients were treated with ISB 830 or placebo.
Actual start date of recruitment	22 Nov 2018
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Poland: 151
Country: Number of subjects enrolled	Czechia: 87
Country: Number of subjects enrolled	Germany: 48
Country: Number of subjects enrolled	United States: 134
Country: Number of subjects enrolled	Canada: 40
Worldwide total number of subjects	460
EEA total number of subjects	286
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	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)	437
From 65 to 84 years	22
85 years and over	1

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	The first patient was enrolled on 22 Nov 2018 and the date of the last visit was 03 August 2021. Overall, 462 patients were enrolled into groups 1-4 in Part 1 and 5-6 in Part 2 (287 in Europe; 175 outside Europe). Results are presented for the full analysis set (N=460).
Pre-assignment
Screening details	Screening occurred within 28 days prior to randomisation. During screening, treatments for AD were withdrawn or modified per protocol. Subjects could be re-screened once (within or outside of the screening period) if they failed the screening evaluation.
Period 1
Period 1 title	Baseline (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator, Monitor, Data analyst, Carer, Assessor
Blinding implementation details	Neither the subject nor Investigator/ Sponsor staff involved in the treatment or clinical evaluation of the subjects were aware of the treatment administered. Since ISB 830 and placebo were not indistinguishable, the study drug was handled/prepared by a designated unblinded study drug administrator on site and was administered by a designated unblinded study team member not involved in the management of study subjects. An unblinded clinical monitor performed the study drug accountability.
Arms
Are arms mutually exclusive	Yes
Arm title	Group 1 (ISB 830 300mg q2w) - Part 1
Arm description	Randomised ISB 830 treatment group, during the 16-week double-blind treatment period of Part 1 of the study.
Arm type	Experimental
Investigational medicinal product name	ISB 830
Investigational medicinal product code
Other name
Pharmaceutical forms	Suspension for injection
Routes of administration	Subcutaneous use
Dosage and administration details	600 mg dose of ISB 830 (2 SC injections) on Day 1. Thereafter, 300 mg ISB 830 (1 SC injection) every 2 weeks (q2w) starting at Day 15.
Arm title	Group 2 (ISB 830 300mg q4w) - Part 1
Arm description	Randomised ISB 830 treatment group, during the 16-week double-blind treatment period of Part 1 of the study.
Arm type	Experimental
Investigational medicinal product name	ISB 830
Investigational medicinal product code
Other name
Pharmaceutical forms	Suspension for injection
Routes of administration	Subcutaneous use
Dosage and administration details	600 mg dose of ISB 830 (2 SC injections) on Day 1. Thereafter, 300 mg ISB 830 (1 SC injection) every 4 weeks (q4w) starting at Day 29. To maintain blinding, placebo (1 SC injection) was administered q4w starting at Day 15.
Arm title	Group 3 (ISB 830 75mg q4w) - Part 1
Arm description	Randomised ISB 830 treatment group, during the 16-week double-blind treatment period of Part 1 of the study.
Arm type	Experimental
Investigational medicinal product name	ISB 830
Investigational medicinal product code
Other name
Pharmaceutical forms	Suspension for injection
Routes of administration	Subcutaneous use
Dosage and administration details	150 mg dose of ISB 830 (2 SC injections) on Day 1. Thereafter, 75 mg ISB 830 (1 SC injection) every 4 weeks (q4w) starting at Day 29. To maintain blinding, placebo (1 SC injection) was administered q4w starting at Day 15.
Arm title	Group 4 (Placebo q2w) - Part 1
Arm description	Randomised ISB 830 treatment group, during the 16-week double-blind treatment period of Part 1 of the study.
Arm type	Placebo
Investigational medicinal product name	Placebo
Investigational medicinal product code
Other name
Pharmaceutical forms	Injection
Routes of administration	Subcutaneous use
Dosage and administration details	Placebo (2 SC injections) on Day 1, followed by q2w dosing with placebo (1 SC injection) starting at Day 15.
Arm title	Group 5 (ISB 830 600mg q2w) - Part 2
Arm description	Randomised ISB 830 treatment group, during the 54-week open-label treatment period of Part 2 of the study.
Arm type	Experimental
Investigational medicinal product name	ISB 830
Investigational medicinal product code
Other name
Pharmaceutical forms	Suspension for injection
Routes of administration	Subcutaneous use
Dosage and administration details	1200 mg dose of ISB 830 (2 SC injections) on Day 1. Thereafter, 600 mg ISB 830 (1 SC injection) every 2 weeks (q2w) starting at Day 15.
Arm title	Group 6 (Placebo q2w) - Part 2
Arm description	Randomised ISB 830 treatment group, during the 54-week open-label treatment period of Part 2 of the study.
Arm type	Placebo
Investigational medicinal product name	Placebo
Investigational medicinal product code
Other name
Pharmaceutical forms	Injection
Routes of administration	Subcutaneous use
Dosage and administration details	Placebo (4 SC injections) on Day 1, followed by q2w dosing with placebo (2 SC injection) starting at Day 15.
Number of subjects in period 1 Group 1 (ISB 830 300mg q2w) - Part 1 Group 2 (ISB 830 300mg q4w) - Part 1 Group 3 (ISB 830 75mg q4w) - Part 1 Group 4 (Placebo q2w) - Part 1 Group 5 (ISB 830 600mg q2w) - Part 2 Group 6 (Placebo q2w) - Part 2 Started 76 78 77 80 75 74 Completed 54 57 42 50 61 60 Not completed 22 21 35 30 14 14      Adverse event, serious fatal - - - - 1 -      Consent withdrawn by subject 15 13 26 21 6 8      Physician decision - 1 1 - 1 -      Adverse event, non-fatal - 1 2 - - 1      Subject decision - - - 1 - 1      Other 3 4 1 4 2 1      Pregnancy - - - 1 - -      Lost to follow-up 3 2 4 2 3 2      Protocol deviation 1 - 1 1 1 1

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Group 1 (ISB 830 300mg q2w) - Part 1
Reporting group description	Randomised ISB 830 treatment group, during the 16-week double-blind treatment period of Part 1 of the study.
Reporting group title	Group 2 (ISB 830 300mg q4w) - Part 1
Reporting group description	Randomised ISB 830 treatment group, during the 16-week double-blind treatment period of Part 1 of the study.
Reporting group title	Group 3 (ISB 830 75mg q4w) - Part 1
Reporting group description	Randomised ISB 830 treatment group, during the 16-week double-blind treatment period of Part 1 of the study.
Reporting group title	Group 4 (Placebo q2w) - Part 1
Reporting group description	Randomised ISB 830 treatment group, during the 16-week double-blind treatment period of Part 1 of the study.
Reporting group title	Group 5 (ISB 830 600mg q2w) - Part 2
Reporting group description	Randomised ISB 830 treatment group, during the 54-week open-label treatment period of Part 2 of the study.
Reporting group title	Group 6 (Placebo q2w) - Part 2
Reporting group description	Randomised ISB 830 treatment group, during the 54-week open-label treatment period of Part 2 of the study.
Reporting group values Group 1 (ISB 830 300mg q2w) - Part 1 Group 2 (ISB 830 300mg q4w) - Part 1 Group 3 (ISB 830 75mg q4w) - Part 1 Group 4 (Placebo q2w) - Part 1 Group 5 (ISB 830 600mg q2w) - Part 2 Group 6 (Placebo q2w) - Part 2 Total Number of subjects 76 78 77 80 75 74 460 Age categorical Units: Subjects     ≥ 18 - <65 71 74 70 78 72 72 437     ≥ 65 5 4 7 2 3 2 23 Age continuous Units: years     arithmetic mean (standard deviation) 40.2 ( 13.10 ) 36.6 ( 14.77 ) 38.4 ( 16.87 ) 36.3 ( 13.05 ) 37.9 ( 13.31 ) 36.0 ( 13.75 ) - Gender categorical Units: Subjects     Female 32 44 41 44 37 47 245     Male 44 34 36 36 38 27 215 Investigator's global assessment (IGA) The Investigator's global assessment (IGA) was an assessment scale used in clinical studies to determine severity of AD and clinical response to treatment based on a 5-point scale ranging from 0 (clear) to 4 (severe). 0 = Clear - No inflammatory signs of atopic dermatitis 4 = Severe disease - Severe erythema and severe papulation/infiltration and Deep/dark red erythema; marked and extensive elevation (papulation/infiltration) Units: Subjects     0 = Clear 0 0 0 0 0 0 0     1 = Almost clear 0 0 0 0 0 0 0     2 = Mild disease 0 0 0 0 0 0 0     3 = Moderate disease 49 48 49 52 48 47 293     4 = Severe disease 27 30 28 28 27 27 167 Number of days with severe pruritus in the past 7 days Number of days with severe pruritus in the past 7 days. Severe pruritus is ≥ 7 on Pruritus NRS. Units: Subjects     <3 days 22 17 17 27 14 18 115     3 days 5 9 4 5 3 2 28     4 days 10 9 10 5 6 6 46     5 days 4 4 9 13 9 12 51     6 days 11 16 17 11 16 14 85     7 days 24 23 20 19 26 22 134     Missing 0 0 0 0 1 0 1 Body surface area Body surface area (BSA) affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]) and was reported as a percentage of all major body sections combined. Units: percent     arithmetic mean (standard deviation) 46.69 ( 21.383 ) 50.82 ( 24.182 ) 46.70 ( 21.175 ) 48.43 ( 22.415 ) 48.43 ( 21.011 ) 52.92 ( 24.786 ) - Pruritus Numerical Rating Scale Baseline Pruritus Numerical Rating Scale (NRS) average score for maximum itch intensity was determined based on the average of daily Pruritus NRS scores for maximum itch intensity (the daily score ranges from 0 to 10) during the 7 days immediately preceding) randomisation. A minimum of 3 daily scores out of the 7 days was required to calculate the baseline average score. Units: NRS score     arithmetic mean (standard deviation) 7.42 ( 1.634 ) 7.53 ( 1.650 ) 7.52 ( 1.639 ) 7.25 ( 1.827 ) 7.44 ( 1.486 ) 7.42 ( 1.698 ) - Eczema Area and Severity Index (EASI) The Eczema Area and Severity Index (EASI) was a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. Four AD disease characteristics were assessed for severity by the Investigator or designee on a scale of “0” (absent) through “3” (severe). In addition, the area of AD involvement was assessed as a percentage by body area of head, trunk, arms, and legs and converted to a score of 0 to 6. Units: EASI score     arithmetic mean (standard deviation) 30.42 ( 14.110 ) 33.84 ( 14.910 ) 28.42 ( 11.602 ) 30.65 ( 13.173 ) 29.86 ( 13.223 ) 31.81 ( 14.340 ) -

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Group 1 (ISB 830 300mg q2w) - Part 1
Reporting group description	Randomised ISB 830 treatment group, during the 16-week double-blind treatment period of Part 1 of the study.
Reporting group title	Group 2 (ISB 830 300mg q4w) - Part 1
Reporting group description	Randomised ISB 830 treatment group, during the 16-week double-blind treatment period of Part 1 of the study.
Reporting group title	Group 3 (ISB 830 75mg q4w) - Part 1
Reporting group description	Randomised ISB 830 treatment group, during the 16-week double-blind treatment period of Part 1 of the study.
Reporting group title	Group 4 (Placebo q2w) - Part 1
Reporting group description	Randomised ISB 830 treatment group, during the 16-week double-blind treatment period of Part 1 of the study.
Reporting group title	Group 5 (ISB 830 600mg q2w) - Part 2
Reporting group description	Randomised ISB 830 treatment group, during the 54-week open-label treatment period of Part 2 of the study.
Reporting group title	Group 6 (Placebo q2w) - Part 2
Reporting group description	Randomised ISB 830 treatment group, during the 54-week open-label treatment period of Part 2 of the study.

End points Top of page

Primary: Percentage change in EASI score Top of page
End point title	Percentage change in EASI score
End point description	Percentage change in EASI score from baseline to Week 16. This was analysed using a mixed-effect model for repeated measures (MMRM). This accounted for the variance-covariance structure between visits and missing data. This model included all scheduled visits for the response variable. The adjusted means for each treatment and the estimated treatment differences for the treatment comparisons were presented together with 95% confidence intervals (CIs), along with P-values for the treatment comparisons. The adjusted means and estimated treatment differences for the treatment comparisons (each ISB 830 group vs placebo group) were also determined with corresponding 95% CIs.
End point type	Primary
End point timeframe	From baseline to Week 16
End point values Group 1 (ISB 830 300mg q2w) - Part 1 Group 2 (ISB 830 300mg q4w) - Part 1 Group 3 (ISB 830 75mg q4w) - Part 1 Group 4 (Placebo q2w) - Part 1 Group 5 (ISB 830 600mg q2w) - Part 2 Group 6 (Placebo q2w) - Part 2 Number of subjects analysed 51 45 39 42 53 51 Units: percent     arithmetic mean (standard deviation) -57.589 ( 36.2014 ) -56.734 ( 32.5395 ) -38.099 ( 39.6857 ) -42.142 ( 38.1945 ) -59.737 ( 27.1176 ) -43.252 ( 41.2404 )
Statistical analysis title	Percentage change in EASI score (Group 1)
Statistical analysis description	The percentage change from baseline (Group 1) in EASI at Week 16 compared to placebo (Group 4). This was an MMRM analysis. The adjusted mean treatment differences for the treatment comparisons were presented together with 95% CIs, along with P-values for the treatment comparisons.
Comparison groups	Group 4 (Placebo q2w) - Part 1 v Group 1 (ISB 830 300mg q2w) - Part 1
Number of subjects included in analysis	93
Analysis specification	Pre-specified
Analysis type	superiority
P-value	= 0.008
Method	Mixed models analysis
Parameter type	LS Mean Difference
Point estimate	-20.192
Confidence interval
level	95%
sides	2-sided
lower limit	-34.944
upper limit	-5.439
Variability estimate	Standard error of the mean
Dispersion value	7.4781
Statistical analysis title	Percentage change in EASI score (Group 2)
Statistical analysis description	The percentage change from baseline (Group 2) in EASI at Week 16 compared to placebo (Group 4). This was an MMRM analysis. The adjusted mean treatment differences for the treatment comparisons were presented together with 95% CIs, along with P-values for the treatment comparisons.
Comparison groups	Group 4 (Placebo q2w) - Part 1 v Group 2 (ISB 830 300mg q4w) - Part 1
Number of subjects included in analysis	87
Analysis specification	Pre-specified
Analysis type	superiority
P-value	= 0.061
Method	Mixed models analysis
Parameter type	LS Mean Difference
Point estimate	-14.439
Confidence interval
level	95%
sides	2-sided
lower limit	-29.552
upper limit	0.674
Variability estimate	Standard error of the mean
Dispersion value	7.6622
Statistical analysis title	Percentage change in EASI score (Group 3)
Statistical analysis description	The percentage change from baseline (Group 3) in EASI at Week 16 compared to placebo (Group 4). This was an MMRM analysis. The adjusted mean treatment differences for the treatment comparisons were presented together with 95% CIs, along with P-values for the treatment comparisons.
Comparison groups	Group 4 (Placebo q2w) - Part 1 v Group 3 (ISB 830 75mg q4w) - Part 1
Number of subjects included in analysis	81
Analysis specification	Pre-specified
Analysis type	superiority
P-value	= 0.691
Method	Mixed models analysis
Parameter type	LS Mean Difference
Point estimate	3.144
Confidence interval
level	95%
sides	2-sided
lower limit	-12.41
upper limit	18.698
Variability estimate	Standard error of the mean
Dispersion value	7.8864
Statistical analysis title	Percentage change in EASI score (Group 5)
Statistical analysis description	The percentage change from baseline (Group 5) in EASI at Week 16 compared to placebo (Group 6). This was an MMRM analysis. The adjusted mean treatment differences for the treatment comparisons were presented together with 95% CIs, along with P-values for the treatment comparisons.
Comparison groups	Group 5 (ISB 830 600mg q2w) - Part 2 v Group 6 (Placebo q2w) - Part 2
Number of subjects included in analysis	104
Analysis specification	Pre-specified
Analysis type	superiority
P-value	= 0.008
Method	Mixed models analysis
Parameter type	LS Mean Difference
Point estimate	-17.199
Confidence interval
level	95%
sides	2-sided
lower limit	-29.895
upper limit	-4.503
Variability estimate	Standard error of the mean
Dispersion value	6.409

Primary: Percentage change in EASI score Top of page

Secondary: EASI-75 Top of page
End point title	EASI-75
End point description	Proportion of subjects with EASI-75 (≥75% improvement from baseline) at Week 16. The analyses were based on the stratified Cochran-Mantel-Haenzsel (CMH) test where randomisation strata (region, disease severity) were used as stratification variables. Pairwise treatment comparisons were made based on the CMH test using the P-value for the general association. The odds ratio and associated CI based on Wald test were provided. The subjects with ≥75% improvement in EASI from baseline at Week 16 were considered as Responders. Any subject who received protocol-specified rescue medication during the blinded treatment period or withdrew from the study before Week 16, was considered a Non-Responder. Also, any subject who was missing a Week 16 efficacy assessment was considered a Non-Responder.
End point type	Secondary
End point timeframe	From baseline to Week 16.
End point values Group 1 (ISB 830 300mg q2w) - Part 1 Group 2 (ISB 830 300mg q4w) - Part 1 Group 3 (ISB 830 75mg q4w) - Part 1 Group 4 (Placebo q2w) - Part 1 Group 5 (ISB 830 600mg q2w) - Part 2 Group 6 (Placebo q2w) - Part 2 Number of subjects analysed 76 78 77 80 75 74 Units: Subjects 18 16 9 9 19 14
Statistical analysis title	EASI-75 (Group 1)
Statistical analysis description	The comparison between Group 1 and placebo (Group 4) were based on the stratified CMH test. Pairwise treatment comparisons were made based on the CMH test using the P-value for the general association. The odds ratio and associated CI based on Wald test were provided.
Comparison groups	Group 1 (ISB 830 300mg q2w) - Part 1 v Group 4 (Placebo q2w) - Part 1
Number of subjects included in analysis	156
Analysis specification	Pre-specified
Analysis type	superiority
P-value	= 0.04
Method	Cochran-Mantel-Haenszel
Parameter type	Odds ratio (OR)
Point estimate	2.492
Confidence interval
level	95%
sides	2-sided
lower limit	1.029
upper limit	6.039
Statistical analysis title	EASI-75 (Group 2)
Statistical analysis description	The comparison between Group 2 and placebo (Group 4) were based on the stratified CMH test. Pairwise treatment comparisons were made based on the CMH test using the P-value for the general association. The odds ratio and associated CI based on Wald test were provided.
Comparison groups	Group 4 (Placebo q2w) - Part 1 v Group 2 (ISB 830 300mg q4w) - Part 1
Number of subjects included in analysis	158
Analysis specification	Pre-specified
Analysis type	superiority
P-value	= 0.109
Method	Cochran-Mantel-Haenszel
Parameter type	Odds ratio (OR)
Point estimate	2.056
Confidence interval
level	95%
sides	2-sided
lower limit	0.843
upper limit	5.012
Statistical analysis title	EASI-75 (Group 3)
Statistical analysis description	The comparison between Group 3 and placebo (Group 4) were based on the stratified CMH test. Pairwise treatment comparisons were made based on the CMH test using the P-value for the general association. The odds ratio and associated CI based on Wald test were provided.
Comparison groups	Group 4 (Placebo q2w) - Part 1 v Group 3 (ISB 830 75mg q4w) - Part 1
Number of subjects included in analysis	157
Analysis specification	Pre-specified
Analysis type	superiority
P-value	= 0.921
Method	Cochran-Mantel-Haenszel
Parameter type	Odds ratio (OR)
Point estimate	1.051
Confidence interval
level	95%
sides	2-sided
lower limit	0.392
upper limit	2.824
Statistical analysis title	EASI-75 (Group 5)
Statistical analysis description	The comparison between Group 5 and placebo (Group 6) were based on the stratified CMH test. Pairwise treatment comparisons were made based on the CMH test using the P-value for the general association. The odds ratio and associated CI based on Wald test were provided.
Comparison groups	Group 5 (ISB 830 600mg q2w) - Part 2 v Group 6 (Placebo q2w) - Part 2
Number of subjects included in analysis	149
Analysis specification	Pre-specified
Analysis type	superiority
P-value	= 0.372
Method	Cochran-Mantel-Haenszel
Parameter type	Odds ratio (OR)
Point estimate	1.444
Confidence interval
level	95%
sides	2-sided
lower limit	0.649
upper limit	3.215

Secondary: EASI-75 Top of page

Secondary: IGA success and IGA reduction Top of page
End point title	IGA success and IGA reduction
End point description	Proportion of subjects achieving IGA success with both IGA 0 or 1 (on a 5-point scale) and an IGA reduction from baseline of ≥2 points at Week 16. The analyses were based on the stratified CMH test where randomisation strata (region, disease severity) were used as stratification variables. Pairwise treatment comparisons were made based on the CMH test using the P-value for the general association. The odds ratio and associated CI based on Wald test were provided. The subjects with both IGA 0 or 1 (on a 5-point scale) and IGA reduction from baseline of ≥2 points at Week 16 were considered as Responders. Any subject who received protocol-specified rescue medication during the Blinded Treatment period or withdrew from the study before Week 16, was considered a Non-Responder. Also, any subject who was missing a Week 16 efficacy assessment were considered a Non-Responder.
End point type	Secondary
End point timeframe	From baseline to Week 16.
End point values Group 1 (ISB 830 300mg q2w) - Part 1 Group 2 (ISB 830 300mg q4w) - Part 1 Group 3 (ISB 830 75mg q4w) - Part 1 Group 4 (Placebo q2w) - Part 1 Group 5 (ISB 830 600mg q2w) - Part 2 Group 6 (Placebo q2w) - Part 2 Number of subjects analysed 76 78 77 80 75 74 Units: Subjects 10 8 5 4 9 4
Statistical analysis title	IGA success and IGA reduction (Group 1)
Statistical analysis description	The comparison between Group 1 and placebo (Group 4) were based on the stratified CMH test. Pairwise treatment comparisons were made based on the CMH test using the P-value for the general association. The odds ratio and associated CI based on Wald test were provided.
Comparison groups	Group 1 (ISB 830 300mg q2w) - Part 1 v Group 4 (Placebo q2w) - Part 1
Number of subjects included in analysis	156
Analysis specification	Pre-specified
Analysis type	superiority
P-value	= 0.073
Method	Cochran-Mantel-Haenszel
Parameter type	Odds ratio (OR)
Point estimate	2.892
Confidence interval
level	95%
sides	2-sided
lower limit	0.867
upper limit	9.647
Statistical analysis title	IGA success and IGA reduction (Group 2)
Statistical analysis description	The comparison between Group 2 and placebo (Group 4) were based on the stratified CMH test. Pairwise treatment comparisons were made based on the CMH test using the P-value for the general association. The odds ratio and associated CI based on Wald test were provided.
Comparison groups	Group 2 (ISB 830 300mg q4w) - Part 1 v Group 4 (Placebo q2w) - Part 1
Number of subjects included in analysis	158
Analysis specification	Pre-specified
Analysis type	superiority
P-value	= 0.206
Method	Cochran-Mantel-Haenszel
Parameter type	Odds ratio (OR)
Point estimate	2.225
Confidence interval
level	95%
sides	2-sided
lower limit	0.635
upper limit	7.791
Statistical analysis title	IGA success and IGA reduction (Group 3)
Statistical analysis description	The comparison between Group 3 and placebo (Group 4) were based on the stratified CMH test. Pairwise treatment comparisons were made based on the CMH test using the P-value for the general association. The odds ratio and associated CI based on Wald test were provided.
Comparison groups	Group 4 (Placebo q2w) - Part 1 v Group 3 (ISB 830 75mg q4w) - Part 1
Number of subjects included in analysis	157
Analysis specification	Pre-specified
Analysis type	superiority
P-value	= 0.659
Method	Cochran-Mantel-Haenszel
Parameter type	Odds ratio (OR)
Point estimate	1.362
Confidence interval
level	95%
sides	2-sided
lower limit	0.346
upper limit	5.358
Statistical analysis title	IGA success and IGA reduction (Group 5)
Statistical analysis description	The comparison between Group 5 and placebo (Group 6) were based on the stratified CMH test. Pairwise treatment comparisons were made based on the CMH test using the P-value for the general association. The odds ratio and associated CI based on Wald test were provided.
Comparison groups	Group 5 (ISB 830 600mg q2w) - Part 2 v Group 6 (Placebo q2w) - Part 2
Number of subjects included in analysis	149
Analysis specification	Pre-specified
Analysis type	superiority
P-value	= 0.155
Method	Cochran-Mantel-Haenszel
Parameter type	Odds ratio (OR)
Point estimate	2.451
Confidence interval
level	95%
sides	2-sided
lower limit	0.695
upper limit	8.641

Secondary: IGA success and IGA reduction Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	From baseline to Week 54.
Adverse event reporting additional description	Adverse events (AEs) were coded using the MedDRA and summarised by system organ class (SOC), preferred term (PT) and treatment group. Subjects were counted only once for each SOC, PT.
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	23.1
Reporting groups
Reporting group title	Group 1 (ISB 830 300mg q2w) - Part 1
Reporting group description	Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1,followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14. Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.
Reporting group title	Group 2 (ISB 830 300mg q4w) - Part 1
Reporting group description	Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14. Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.
Reporting group title	Group 3 (ISB 830 75mg q4w) - Part 1
Reporting group description	Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14. Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66
Reporting group title	Group 4 (Placebo q2w) - Part 1 - blinded
Reporting group description	Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.
Reporting group title	Group 5 (ISB 830 600mg q2w) - Part 2
Reporting group description	Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14. Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.
Reporting group title	Group 6 (Placebo q2w) - Part 2 - blinded
Reporting group description	Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.
Reporting group title	Group 7 (placebo, open-label) - Part 1
Reporting group description	Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66. Note, this is a subset of patients in Group 4.
Reporting group title	Group 8 (Placebo open-label) - Part 2
Reporting group description	Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66. Note, this is a subset of patients in Group 6.
Serious adverse events Group 1 (ISB 830 300mg q2w) - Part 1 Group 2 (ISB 830 300mg q4w) - Part 1 Group 3 (ISB 830 75mg q4w) - Part 1 Group 4 (Placebo q2w) - Part 1 - blinded Group 5 (ISB 830 600mg q2w) - Part 2 Group 6 (Placebo q2w) - Part 2 - blinded Group 7 (placebo, open-label) - Part 1 Group 8 (Placebo open-label) - Part 2 Total subjects affected by serious adverse events      subjects affected / exposed 4 / 76 (5.26%) 6 / 78 (7.69%) 4 / 77 (5.19%) 1 / 80 (1.25%) 1 / 75 (1.33%) 0 / 74 (0.00%) 2 / 60 (3.33%) 2 / 67 (2.99%)      number of deaths (all causes) 0 0 0 0 1 0 0 0      number of deaths resulting from adverse events 0 0 0 0 1 0 0 0 Neoplasms benign, malignant and unspecified (incl cysts and polyps) Keratoacanthoma      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Uterine leiomyoma      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Adenocarcinoma of colon      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Injury, poisoning and procedural complications Gun shot wound      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Ligament rupture      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Femur fracture      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Vascular disorders Hypertension      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 Cardiac disorders Atrial fibrillation      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Pregnancy, puerperium and perinatal conditions Abortion spontaneous complete      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 General disorders and administration site conditions Eye complication associated with device      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Pyrexia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Blood and lymphatic system disorders Pernicious anaemia      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Eye disorders Chorioretinopathy      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Skin and subcutaneous tissue disorders Dermatitis atopic      subjects affected / exposed 2 / 76 (2.63%) 2 / 78 (2.56%) 1 / 77 (1.30%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences causally related to treatment / all 2 / 2 0 / 2 1 / 1 0 / 1 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Infections and infestations Viral infection      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences causally related to treatment / all 0 / 0 0 / 0 1 / 1 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 Metabolism and nutrition disorders Metabolic acidosis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0 0 / 0
Frequency threshold for reporting non-serious adverse events: 1%
Non-serious adverse events Group 1 (ISB 830 300mg q2w) - Part 1 Group 2 (ISB 830 300mg q4w) - Part 1 Group 3 (ISB 830 75mg q4w) - Part 1 Group 4 (Placebo q2w) - Part 1 - blinded Group 5 (ISB 830 600mg q2w) - Part 2 Group 6 (Placebo q2w) - Part 2 - blinded Group 7 (placebo, open-label) - Part 1 Group 8 (Placebo open-label) - Part 2 Total subjects affected by non serious adverse events      subjects affected / exposed 68 / 76 (89.47%) 56 / 78 (71.79%) 64 / 77 (83.12%) 57 / 80 (71.25%) 65 / 75 (86.67%) 37 / 74 (50.00%) 43 / 60 (71.67%) 38 / 67 (56.72%) Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign breast neoplasm      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Skin papilloma      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Uterine leiomyoma      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Vascular disorders Hypertension      subjects affected / exposed 5 / 76 (6.58%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 3 / 75 (4.00%) 1 / 74 (1.35%) 2 / 60 (3.33%) 1 / 67 (1.49%)      occurrences all number 5 1 0 0 3 1 2 1 Flushing      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Thrombophlebitis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 General disorders and administration site conditions Fatigue      subjects affected / exposed 2 / 76 (2.63%) 5 / 78 (6.41%) 1 / 77 (1.30%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 2 8 1 0 3 0 1 0 Application site reaction      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 Asthenia      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 1 1 0 0 0 1 1 0 Chest discomfort      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Chest pain      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 1 / 77 (1.30%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 1 1 0 0 0 0 Chills      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Face oedema      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Facial pain      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Feeling cold      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 1 0 0 0 0 Feeling hot      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Influenza like illness      subjects affected / exposed 1 / 76 (1.32%) 3 / 78 (3.85%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 5 1 0 0 0 0 0 Injection site bruising      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 1 0 0 0 Injection site erythema      subjects affected / exposed 1 / 76 (1.32%) 3 / 78 (3.85%) 0 / 77 (0.00%) 0 / 80 (0.00%) 2 / 75 (2.67%) 1 / 74 (1.35%) 2 / 60 (3.33%) 1 / 67 (1.49%)      occurrences all number 1 3 0 0 5 2 3 1 Injection site haematoma      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 1 0 0 0 Injection site induration      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Injection site oedema      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Injection site pain      subjects affected / exposed 1 / 76 (1.32%) 2 / 78 (2.56%) 1 / 77 (1.30%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 1 2 1 0 1 0 1 0 Injection site pruritus      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 1 0 Injection site rash      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 Injection site reaction      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 2 / 77 (2.60%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 5 0 1 0 0 1 Injection site swelling      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 1 0 0 1 0 0 0 Injection site urticaria      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 1 / 77 (1.30%) 1 / 80 (1.25%) 2 / 75 (2.67%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 1 1 3 0 0 0 Malaise      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Oedema peripheral      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 2 / 77 (2.60%) 0 / 80 (0.00%) 1 / 75 (1.33%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 2 0 1 1 0 0 Pain      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 Peripheral swelling      subjects affected / exposed 2 / 76 (2.63%) 2 / 78 (2.56%) 1 / 77 (1.30%) 1 / 80 (1.25%) 1 / 75 (1.33%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 3 3 1 1 1 1 0 0 Pyrexia      subjects affected / exposed 2 / 76 (2.63%) 1 / 78 (1.28%) 2 / 77 (2.60%) 0 / 80 (0.00%) 0 / 75 (0.00%) 2 / 74 (2.70%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 2 1 2 0 0 2 1 0 Therapeutic response unexpected      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Immune system disorders Allergy to animal      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 3 0 0 0 0 0 0 Allergy to arthropod bite      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Allergy to arthropod sting      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Drug hypersensitivity      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Food allergy      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 Hypersensitivity      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 3 0 0 0 0 0 0 Seasonal allergy      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 1 / 80 (1.25%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 1 2 0 0 0 Reproductive system and breast disorders Breast inflammation      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Breast mass      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 2 / 67 (2.99%)      occurrences all number 0 0 0 0 0 0 0 2 Breast pain      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Breast tenderness      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Cervix inflammation      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Dysmenorrhoea      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 1 / 80 (1.25%) 2 / 75 (2.67%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 1 4 0 0 0 Menstrual disorder      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Ovarian cyst      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 Ovarian disorder      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Premature menopause      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Sexual dysfunction      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Uterine cervix stenosis      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Uterine haemorrhage      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Vaginal haemorrhage      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Respiratory, thoracic and mediastinal disorders Asthma      subjects affected / exposed 2 / 76 (2.63%) 4 / 78 (5.13%) 3 / 77 (3.90%) 1 / 80 (1.25%) 2 / 75 (2.67%) 0 / 74 (0.00%) 1 / 60 (1.67%) 1 / 67 (1.49%)      occurrences all number 2 6 4 1 2 0 1 1 Cough      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 4 / 77 (5.19%) 2 / 80 (2.50%) 3 / 75 (4.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 1 4 2 4 0 0 0 Catarrh      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 1 0 0 0 Dysphonia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Dyspnoea      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 1 / 77 (1.30%) 1 / 80 (1.25%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 1 1 1 0 0 0 Epistaxis      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 1 0 0 0 0 0 0 Nasal congestion      subjects affected / exposed 3 / 76 (3.95%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 3 0 0 0 0 0 0 0 Nasal septum disorder      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Oropharyngeal pain      subjects affected / exposed 2 / 76 (2.63%) 0 / 78 (0.00%) 2 / 77 (2.60%) 1 / 80 (1.25%) 3 / 75 (4.00%) 1 / 74 (1.35%) 4 / 60 (6.67%) 1 / 67 (1.49%)      occurrences all number 2 0 2 1 3 2 4 2 Productive cough      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Reflux laryngitis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Rhinitis allergic      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 2 / 77 (2.60%) 0 / 80 (0.00%) 3 / 75 (4.00%) 2 / 74 (2.70%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 1 1 2 0 4 2 1 0 Rhinorrhoea      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 1 / 77 (1.30%) 0 / 80 (0.00%) 2 / 75 (2.67%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 1 1 0 2 0 0 1 Sinus congestion      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 1 0 0 Throat irritation      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Upper respiratory tract inflammation      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 1 0 0 0 Psychiatric disorders Alcohol abuse      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 2 0 0 0 Anxiety      subjects affected / exposed 2 / 76 (2.63%) 1 / 78 (1.28%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 2 1 0 1 0 0 1 0 Attention deficit hyperactivity disorder      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Bipolar disorder      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Depression      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 2 / 77 (2.60%) 1 / 80 (1.25%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 1 2 1 1 0 0 0 Initial insomnia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Insomnia      subjects affected / exposed 0 / 76 (0.00%) 2 / 78 (2.56%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 3 1 0 0 0 0 0 Mixed anxiety and depressive disorder      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Nervousness      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Panic attack      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Investigations Alanine aminotransferase increased      subjects affected / exposed 0 / 76 (0.00%) 2 / 78 (2.56%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 2 0 0 0 0 0 0 Aspartate aminotransferase increased      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 1 0 0 1 Bacterial test positive      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Blood bicarbonate decreased      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 1 0 0 0 0 Blood bilirubin increased      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Blood creatinine increased      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 2 / 77 (2.60%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 1 0 2 1 0 0 2 0 Blood glucose increased      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Blood iron decreased      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Blood pressure increased      subjects affected / exposed 2 / 76 (2.63%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 2 0 0 0 0 1 1 0 Blood triglycerides increased      subjects affected / exposed 2 / 76 (2.63%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 2 0 0 0 0 0 0 0 Blood urine present      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 Body temperature increased      subjects affected / exposed 0 / 76 (0.00%) 2 / 78 (2.56%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 2 0 0 1 0 1 0 C-reactive protein increased      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 Cardiac murmur      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Gamma-glutamyltransferase increased      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Glucose urine present      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Haemoglobin decreased      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Haemoglobin urine present      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Hepatic enzyme increased      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 4 0 1 0 0 0 0 0 Liver function test increased      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Lymphocyte count decreased      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 Neutrophil count decreased      subjects affected / exposed 0 / 76 (0.00%) 2 / 78 (2.56%) 0 / 77 (0.00%) 1 / 80 (1.25%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 2 0 3 1 0 0 0 Platelet count increased      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 2 0 0 Protein urine present      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Red blood cell count decreased      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Red blood cells urine positive      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 Streptococcus test positive      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Transaminases increased      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Urinary casts present      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 Urine ketone body present      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Urine leukocyte esterase      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 Urine leukocyte esterase positive      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Weight increased      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 1 0 1 0 0 0 0 1 White blood cell count increased      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 1 / 80 (1.25%) 0 / 75 (0.00%) 2 / 74 (2.70%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 1 0 3 0 0 White blood cells urine positive      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Injury, poisoning and procedural complications Accidental overdose      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 2 / 77 (2.60%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 4 0 0 0 0 0 Alcohol poisoning      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Arthropod bite      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 3 / 75 (4.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 1 0 4 0 0 0 Burns second degree      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 1 0 Contusion      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 Epicondylitis      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 2 0 0 0 0 0 0 0 Hand fracture      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 1 1 Injection related reaction      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 4 0 0 0 0 0 0 0 Joint injury      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 3 / 67 (4.48%)      occurrences all number 0 0 0 0 0 0 0 3 Ligament injury      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Ligament sprain      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 2 / 77 (2.60%) 1 / 80 (1.25%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 2 1 1 0 0 0 Limb injury      subjects affected / exposed 3 / 76 (3.95%) 0 / 78 (0.00%) 2 / 77 (2.60%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 3 0 2 0 0 0 0 0 Meniscus injury      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Nail injury      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Muscle strain      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 1 0 Overdose      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 1 / 80 (1.25%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 1 1 0 0 0 Procedural pain      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 1 / 77 (1.30%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 1 0 1 0 0 0 Rib fracture      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Road traffic accident      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 Skin abrasion      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 Skin laceration      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 1 0 Tooth fracture      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 1 0 0 0 Transfusion related complication      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Vaccination complication      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 1 0 0 1 Wrist fracture      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Cardiac disorders Bradycardia      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Left ventricular hypertrophy      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Tachycardia      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 2 / 77 (2.60%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 2 0 0 1 0 0 Ventricular extrasystoles      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 1 0 0 0 0 0 0 Nervous system disorders Headache      subjects affected / exposed 8 / 76 (10.53%) 7 / 78 (8.97%) 4 / 77 (5.19%) 8 / 80 (10.00%) 6 / 75 (8.00%) 5 / 74 (6.76%) 5 / 60 (8.33%) 7 / 67 (10.45%)      occurrences all number 10 14 4 9 11 5 7 8 Ageusia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Anosmia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Aphonia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 Dizziness      subjects affected / exposed 2 / 76 (2.63%) 2 / 78 (2.56%) 2 / 77 (2.60%) 0 / 80 (0.00%) 0 / 75 (0.00%) 2 / 74 (2.70%) 1 / 60 (1.67%) 1 / 67 (1.49%)      occurrences all number 2 2 2 0 0 2 1 3 Dysaesthesia      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 1 0 0 0 0 0 0 Hypoaesthesia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Loss of consciousness      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Migraine      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 1 / 80 (1.25%) 1 / 75 (1.33%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 1 1 1 0 0 Nerve compression      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Paraesthesia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 2 / 77 (2.60%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 2 0 0 0 0 0 Presyncope      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 1 0 0 0 0 Sciatica      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 1 / 77 (1.30%) 0 / 80 (0.00%) 1 / 75 (1.33%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 1 0 1 1 0 0 Sinus headache      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Somnolence      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Tension headache      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Thoracic spinal cord paralysis      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Blood and lymphatic system disorders Anaemia      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 1 0 0 0 Blood loss anaemia      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 1 0 0 0 Iron deficiency anaemia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Lymphadenopathy      subjects affected / exposed 0 / 76 (0.00%) 2 / 78 (2.56%) 2 / 77 (2.60%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 2 2 0 1 0 0 1 Lymphopenia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 2 / 80 (2.50%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 2 0 0 0 0 Neutropenia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 1 0 0 1 Thrombocytosis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Ear and labyrinth disorders Deafness unilateral      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Ear pain      subjects affected / exposed 2 / 76 (2.63%) 0 / 78 (0.00%) 2 / 77 (2.60%) 1 / 80 (1.25%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 2 0 3 1 1 0 0 0 Ear swelling      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 2 0 0 0 0 External ear inflammation      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 2 / 80 (2.50%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 2 0 0 0 0 External ear pain      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Middle ear inflammation      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 Ear lobe infection      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 Eye disorders Blepharitis      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Cataract      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Chalazion      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 2 / 80 (2.50%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 2 0 0 2 0 Conjunctivitis allergic      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 1 0 0 1 0 0 1 Conjunctival hyperaemia      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Eye haemorrhage      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 2 0 0 0 0 0 0 0 Eye irritation      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 Eyelid margin crusting      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Eyelid oedema      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Keratitis      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Photophobia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Swelling of eyelid      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 2 0 0 0 0 0 Visual impairment      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 1 0 0 1 Gastrointestinal disorders Abdominal pain      subjects affected / exposed 1 / 76 (1.32%) 3 / 78 (3.85%) 0 / 77 (0.00%) 0 / 80 (0.00%) 4 / 75 (5.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 3 0 0 4 0 0 0 Diarrhoea      subjects affected / exposed 4 / 76 (5.26%) 2 / 78 (2.56%) 6 / 77 (7.79%) 1 / 80 (1.25%) 3 / 75 (4.00%) 3 / 74 (4.05%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 6 2 6 1 3 3 0 1 Abdominal discomfort      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 1 0 0 0 0 0 0 Abdominal pain lower      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Abdominal pain upper      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 2 1 0 0 1 0 0 Aphthous ulcer      subjects affected / exposed 0 / 76 (0.00%) 2 / 78 (2.56%) 1 / 77 (1.30%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 2 1 0 2 0 0 0 Cheilitis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 Constipation      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 2 / 77 (2.60%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 2 0 0 0 0 0 Dental caries      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Dry mouth      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Dyspepsia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 Gastritis      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 1 / 77 (1.30%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 1 0 1 0 0 0 Gastrointestinal inflammation      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Gastrooesophageal reflux disease      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 1 / 67 (1.49%)      occurrences all number 0 1 0 0 0 0 1 1 Gastrooesophageal sphincter insufficiency      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Haematochezia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 Haemorrhoidal haemorrhage      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Haemorrhoids      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Nausea      subjects affected / exposed 3 / 76 (3.95%) 3 / 78 (3.85%) 2 / 77 (2.60%) 2 / 80 (2.50%) 2 / 75 (2.67%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 3 5 3 2 2 0 0 0 Odynophagia      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Reflux gastritis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Stomatitis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Toothache      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 1 0 1 0 1 0 0 1 Tooth impacted      subjects affected / exposed 2 / 76 (2.63%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 3 0 0 0 0 0 0 0 Vomiting      subjects affected / exposed 1 / 76 (1.32%) 3 / 78 (3.85%) 1 / 77 (1.30%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 1 4 1 1 0 0 2 0 Hepatobiliary disorders Hepatic function abnormal      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 Hepatic steatosis      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Hypertransaminasaemia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Skin and subcutaneous tissue disorders Dermatitis atopic      subjects affected / exposed 17 / 76 (22.37%) 24 / 78 (30.77%) 21 / 77 (27.27%) 17 / 80 (21.25%) 26 / 75 (34.67%) 12 / 74 (16.22%) 12 / 60 (20.00%) 11 / 67 (16.42%)      occurrences all number 20 45 29 20 39 15 12 13 Pruritus      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 4 / 77 (5.19%) 1 / 80 (1.25%) 2 / 75 (2.67%) 2 / 74 (2.70%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 1 5 2 3 2 0 1 Acne      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 1 1 0 0 1 0 Actinic keratosis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Alopecia      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 2 / 77 (2.60%) 3 / 80 (3.75%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 1 2 3 1 0 0 0 Alopecia areata      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Angioedema      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Blister      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Dermatitis allergic      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Dermatitis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Dermatitis contact      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 1 / 77 (1.30%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 1 1 0 0 0 0 Dermatitis exfoliative generalised      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 1 1 0 0 0 1 1 0 Dyshidrotic eczema      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 1 0 0 0 Ecchymosis      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Erythema      subjects affected / exposed 2 / 76 (2.63%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 2 / 75 (2.67%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 2 0 0 0 2 0 0 0 Hyperhidrosis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Onycholysis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 3 0 1 0 Photodermatosis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Pityriasis rosea      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Pruritus allergic      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Psoriasis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Purpura      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Rash      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 1 0 0 0 Rash erythematous      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Rash follicular      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Rash papular      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 1 / 77 (1.30%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 1 1 0 0 0 0 Rosacea      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Seborrhoeic dermatitis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Skin burning sensation      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Skin exfoliation      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Skin induration      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Skin fissures      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Swelling face      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Solar urticaria      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Urticaria      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 2 / 80 (2.50%) 2 / 75 (2.67%) 1 / 74 (1.35%) 0 / 60 (0.00%) 2 / 67 (2.99%)      occurrences all number 0 0 1 2 2 1 0 2 Renal and urinary disorders Haematuria      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 1 0 0 0 Haemoglobinuria      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Urine abnormality      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Endocrine disorders Autoimmune thyroiditis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Hypothyroidism      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 1 0 0 0 0 0 0 1 Musculoskeletal and connective tissue disorders Arthralgia      subjects affected / exposed 6 / 76 (7.89%) 2 / 78 (2.56%) 4 / 77 (5.19%) 0 / 80 (0.00%) 2 / 75 (2.67%) 0 / 74 (0.00%) 3 / 60 (5.00%) 0 / 67 (0.00%)      occurrences all number 7 3 4 0 2 0 3 0 Arthritis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 2 / 75 (2.67%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 2 0 0 0 Back pain      subjects affected / exposed 3 / 76 (3.95%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 2 / 75 (2.67%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 3 0 0 1 2 0 0 1 Bursitis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Groin pain      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Joint swelling      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 2 / 77 (2.60%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 2 0 1 0 0 0 Ligamentitis      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Muscle spasms      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Musculoskeletal stiffness      subjects affected / exposed 2 / 76 (2.63%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 2 1 0 0 0 0 0 0 Muscle tightness      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Musculoskeletal discomfort      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Musculoskeletal pain      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Myalgia      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 3 0 1 0 1 0 0 1 Neck pain      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 2 / 75 (2.67%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 2 0 0 0 Pain in extremity      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 2 / 77 (2.60%) 1 / 80 (1.25%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 3 1 1 0 0 0 Pain in jaw      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Scleroderma      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 Spinal osteoarthritis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Spinal pain      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 0 / 77 (0.00%) 2 / 80 (2.50%) 0 / 75 (0.00%) 1 / 74 (1.35%) 1 / 60 (1.67%) 1 / 67 (1.49%)      occurrences all number 1 2 0 2 0 1 2 1 Synovitis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Tendon pain      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Tendonitis      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 2 / 75 (2.67%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 2 0 0 0 Infections and infestations Bronchitis      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 3 / 77 (3.90%) 0 / 80 (0.00%) 4 / 75 (5.33%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 1 0 3 0 4 0 1 0 Influenza      subjects affected / exposed 4 / 76 (5.26%) 5 / 78 (6.41%) 1 / 77 (1.30%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 2 / 60 (3.33%) 0 / 67 (0.00%)      occurrences all number 5 5 2 0 1 0 2 0 Nasopharyngitis      subjects affected / exposed 16 / 76 (21.05%) 15 / 78 (19.23%) 10 / 77 (12.99%) 7 / 80 (8.75%) 12 / 75 (16.00%) 7 / 74 (9.46%) 9 / 60 (15.00%) 8 / 67 (11.94%)      occurrences all number 19 21 15 8 14 10 11 8 Oral herpes      subjects affected / exposed 2 / 76 (2.63%) 3 / 78 (3.85%) 6 / 77 (7.79%) 2 / 80 (2.50%) 2 / 75 (2.67%) 2 / 74 (2.70%) 4 / 60 (6.67%) 3 / 67 (4.48%)      occurrences all number 3 3 10 3 2 2 7 5 Upper respiratory tract infection      subjects affected / exposed 12 / 76 (15.79%) 8 / 78 (10.26%) 13 / 77 (16.88%) 4 / 80 (5.00%) 6 / 75 (8.00%) 5 / 74 (6.76%) 8 / 60 (13.33%) 1 / 67 (1.49%)      occurrences all number 16 13 17 4 7 6 9 2 Urinary tract infection      subjects affected / exposed 3 / 76 (3.95%) 4 / 78 (5.13%) 4 / 77 (5.19%) 4 / 80 (5.00%) 3 / 75 (4.00%) 2 / 74 (2.70%) 4 / 60 (6.67%) 1 / 67 (1.49%)      occurrences all number 4 4 4 4 5 2 5 1 Abscess limb      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Abscess oral      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Acarodermatitis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 Acne pustular      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Asymptomatic bacteriuria      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 1 0 0 0 0 0 Asymptomatic COVID-19      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Bacterial blepharitis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Bacterial vaginosis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 2 0 0 2 0 Bacterial vulvovaginitis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Bacteriuria      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 COVID-19      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 2 / 75 (2.67%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 2 0 0 1 Cellulitis      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 1 / 77 (1.30%) 1 / 80 (1.25%) 2 / 75 (2.67%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 2 2 1 1 2 0 1 0 Chest wall abscess      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Chronic sinusitis      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 2 0 0 0 0 0 0 0 Conjunctivitis      subjects affected / exposed 2 / 76 (2.63%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 2 / 75 (2.67%) 1 / 74 (1.35%) 1 / 60 (1.67%) 1 / 67 (1.49%)      occurrences all number 2 1 0 0 2 1 1 1 Conjunctivitis bacterial      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Cystitis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 2 1 0 0 Ear infection      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 1 / 77 (1.30%) 1 / 80 (1.25%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 1 1 0 1 0 0 Eczema herpeticum      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 1 0 0 0 0 0 Eczema impetiginous      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 1 0 1 0 0 0 0 Eczema infected      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 1 0 0 Enteritis infectious      subjects affected / exposed 0 / 76 (0.00%) 2 / 78 (2.56%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 2 0 0 0 0 0 0 Enterobiasis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Epiglottitis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 1 0 0 Erysipelas      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Eyelid infection      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Folliculitis      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 0 / 77 (0.00%) 2 / 80 (2.50%) 1 / 75 (1.33%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 1 1 0 2 1 0 2 0 Furuncle      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 1 0 1 0 0 0 1 0 Gastroenteritis      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 0 / 77 (0.00%) 1 / 80 (1.25%) 2 / 75 (2.67%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 1 2 0 1 2 0 0 1 Gastroenteritis viral      subjects affected / exposed 0 / 76 (0.00%) 2 / 78 (2.56%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 2 / 60 (3.33%) 0 / 67 (0.00%)      occurrences all number 0 3 1 0 0 0 2 0 Gastrointestinal infection      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Gastrointestinal viral infection      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 2 / 80 (2.50%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 2 0 0 0 0 Genital herpes      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Genital infection female      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Gingivitis      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 1 0 0 0 Herpes ophthalmic      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 1 0 0 0 Herpes simplex      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 3 / 77 (3.90%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 1 4 0 1 0 0 1 Herpes zoster      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 1 0 0 0 0 0 0 Hordeolum      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 1 / 60 (1.67%) 1 / 67 (1.49%)      occurrences all number 0 0 1 0 1 0 1 1 Impetigo      subjects affected / exposed 2 / 76 (2.63%) 0 / 78 (0.00%) 1 / 77 (1.30%) 1 / 80 (1.25%) 3 / 75 (4.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 2 0 1 2 4 0 0 0 Infection      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Laryngitis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 2 / 60 (3.33%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 1 2 0 Localised infection      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Ophthalmic herpes simplex      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 1 0 0 Oral candidiasis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Otitis externa      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 3 0 0 0 0 0 0 0 Otitis externa bacterial      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Paronychia      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Peritonsillar abscess      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 Periodontitis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 0 0 0 1 Pharyngitis      subjects affected / exposed 0 / 76 (0.00%) 2 / 78 (2.56%) 0 / 77 (0.00%) 2 / 80 (2.50%) 2 / 75 (2.67%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 2 0 2 2 0 1 0 Pharyngitis streptococcal      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 1 0 0 0 Pneumonia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Pulpitis dental      subjects affected / exposed 3 / 76 (3.95%) 0 / 78 (0.00%) 1 / 77 (1.30%) 1 / 80 (1.25%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 3 0 1 1 1 0 0 0 Pyuria      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Rash pustular      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Respiratory tract infection      subjects affected / exposed 2 / 76 (2.63%) 2 / 78 (2.56%) 1 / 77 (1.30%) 2 / 80 (2.50%) 2 / 75 (2.67%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 2 3 1 2 2 0 1 0 Rhinitis      subjects affected / exposed 0 / 76 (0.00%) 2 / 78 (2.56%) 1 / 77 (1.30%) 0 / 80 (0.00%) 2 / 75 (2.67%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 2 1 0 2 0 0 0 Sinusitis      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 2 / 77 (2.60%) 0 / 80 (0.00%) 1 / 75 (1.33%) 1 / 74 (1.35%) 3 / 60 (5.00%) 0 / 67 (0.00%)      occurrences all number 0 1 2 0 1 1 3 0 Skin bacterial infection      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 1 / 77 (1.30%) 0 / 80 (0.00%) 1 / 75 (1.33%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 1 0 1 1 0 0 Skin candida      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Skin infection      subjects affected / exposed 2 / 76 (2.63%) 2 / 78 (2.56%) 1 / 77 (1.30%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 2 2 1 1 0 0 0 0 Staphylococcal infection      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Staphylococcal skin infection      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 2 2 0 0 0 1 Subcutaneous abscess      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 1 0 1 0 0 0 Superinfection      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 1 0 Superinfection bacterial      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Tinea pedis      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 1 0 0 0 0 0 1 Tonsillitis      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 2 / 75 (2.67%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 1 0 1 0 3 0 0 1 Testicular abscess      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Tooth abscess      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 1 0 0 0 Tooth infection      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Trichomoniasis      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 Vaginal infection      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 2 / 67 (2.99%)      occurrences all number 0 0 0 0 1 0 0 3 Varicella zoster virus infection      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 Viral infection      subjects affected / exposed 1 / 76 (1.32%) 2 / 78 (2.56%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 2 / 60 (3.33%) 0 / 67 (0.00%)      occurrences all number 1 2 0 1 0 0 2 0 Viral pharyngitis      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 1 0 0 0 0 0 Viral upper respiratory tract infection      subjects affected / exposed 3 / 76 (3.95%) 1 / 78 (1.28%) 1 / 77 (1.30%) 1 / 80 (1.25%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 3 2 1 1 1 0 0 1 Vulvovaginal candidiasis      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Vulvovaginal mycotic infection      subjects affected / exposed 1 / 76 (1.32%) 1 / 78 (1.28%) 1 / 77 (1.30%) 2 / 80 (2.50%) 0 / 75 (0.00%) 1 / 74 (1.35%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 2 1 2 0 1 0 0 Ear lobe infection      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 1 0 0 0 0 Metabolism and nutrition disorders Dehydration      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Diabetes mellitus      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 1 0 0 0 0 0 0 0 Dyslipidaemia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 Gout      subjects affected / exposed 1 / 76 (1.32%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 2 0 0 0 0 0 0 0 Histamine intolerance      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 0 0 0 0 0 0 Hyperglycaemia      subjects affected / exposed 0 / 76 (0.00%) 1 / 78 (1.28%) 1 / 77 (1.30%) 1 / 80 (1.25%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 1 1 1 0 0 0 0 Hypercholesterolaemia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 1 / 67 (1.49%)      occurrences all number 0 0 0 0 1 0 0 1 Hyperkalaemia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Hyperlipidaemia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 1 / 80 (1.25%) 2 / 75 (2.67%) 0 / 74 (0.00%) 1 / 60 (1.67%) 1 / 67 (1.49%)      occurrences all number 0 0 0 3 2 0 1 1 Hypertriglyceridaemia      subjects affected / exposed 2 / 76 (2.63%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 1 / 60 (1.67%) 1 / 67 (1.49%)      occurrences all number 3 0 0 0 1 0 1 1 Hyperuricaemia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 1 0 0 0 Hypokalaemia      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Increased appetite      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 1 / 77 (1.30%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 1 0 0 0 0 0 Vitamin B12 deficiency      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 0 / 75 (0.00%) 0 / 74 (0.00%) 1 / 60 (1.67%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 0 0 1 0 Vitamin D deficiency      subjects affected / exposed 0 / 76 (0.00%) 0 / 78 (0.00%) 0 / 77 (0.00%) 0 / 80 (0.00%) 1 / 75 (1.33%) 0 / 74 (0.00%) 0 / 60 (0.00%) 0 / 67 (0.00%)      occurrences all number 0 0 0 0 2 0 0 0