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Clinical Trial Results:
A phase III Safety and Efficacy Study of ALZT-OP1 in Subjects with Evidence of Early Alzheimer’s Disease.

Summary
EudraCT number	2015-002147-34
Trial protocol	HU CZ BG PL
Global end of trial date	13 Nov 2020

Results information
Results version number	v1(current)
This version publication date	16 Jun 2022
First version publication date	16 Jun 2022
Other versions

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

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Trial information

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Sponsor protocol code

AZT-001

ISRCTN number

US NCT number

NCT02547818

WHO universal trial number (UTN)

Sponsor organisation name

AZTherapies, Inc.

Sponsor organisation address

200 Clarendon Street, 17th Floor, Boston, United States, 02116

Public contact

Information Desk, AZTherapies, Inc., +1 (617) 318-3411, info@aztherapies.com

Scientific contact

Information Desk, AZTherapies, Inc., +1 (617) 318-3411, info@aztherapies.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

13 Nov 2020

Is this the analysis of the primary completion data?

Yes

Primary completion date

13 Nov 2020

Global end of trial reached?

Yes

Global end of trial date

13 Nov 2020

Was the trial ended prematurely?

Main objective of the trial

To evaluate the safety and tolerability of a combination treatment regimen (ALZT-OP1) of oral inhaled cromolyn, plus oral ibuprofen tablets, compared to each of the single component groups. To evaluate the efficacy by Clinical Dementia Rating-Sum of Boxes (CDR-SB) assessment of a combination treatment regimen (ALZT-OP1) of oral inhaled cromolyn, plus oral ibuprofen tablets, compared to each of the single component groups. To determine whether this combination treatment regimen slows down, arrests or reverses cognitive and functional decline in subjects with evidence of early Alzheimer’s Disease (AD).

Protection of trial subjects

Informed consent by the study participant and the requirement of a qualified study partner that also provided informed consent. The Data and Safety Monitoring Board comprising of independent group of experts met at regular intervals to review the safety data while the trial was ongoing.

Background therapy

Evidence for comparator

Actual start date of recruitment

21 Sep 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 72

Country: Number of subjects enrolled

Bulgaria: 17

Country: Number of subjects enrolled

Czechia: 108

Country: Number of subjects enrolled

Hungary: 22

Country: Number of subjects enrolled

Canada: 57

Country: Number of subjects enrolled

United States: 341

Country: Number of subjects enrolled

Australia: 2

Worldwide total number of subjects

619

EEA total number of subjects

219

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

135

From 65 to 84 years

484

85 years and over

Subject disposition

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Recruitment details

Screening details

Subjects were screened against the inclusion/exclusion criteria of the study protocol. Key inclusion criteria included: 55-79 years old (inclusive); evidence of early AD as defined; CSF biomarker results consistent with early AD, including CSF Aβ-42 levels ≥180 pg/ml and ≤690 pg/ml; CDR-Global = 0.5; Memory Box score must be at least 0.5.

Period 1 title

Overall trial (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

This was a placebo-controlled, double blind, randomized study. To maintain blinding, study drug and placebo were prepared to look identical so that the subject, investigator, study staff, monitor, and sponsor remain blinded to treatment assignment. The study drug/placebo had unique coding to link subject assignments to actual treatment assignments at the end of the study. All investigators, subjects, site personnel, sponsor and CRO study team, were blinded to the medication codes.

Are arms mutually exclusive

Yes

Group 1

Arm description

ALZT-OP1a (q.d. inhalation of active cromolyn via DPI + q.d. oral placebo tablet)

Arm type

single active component - cromolyn

Investigational medicinal product name

cromolyn

Investigational medicinal product code

ALZT-OP1a

Other name

Pharmaceutical forms

Inhalation powder, hard capsule

Routes of administration

Inhalation use

Dosage and administration details

ALZT-OP1a (cromolyn) was supplied as a 17.1 mg powder blend encapsulated for administration via oral inhalation using a mono-dose dry powder inhaler (DPI) for once daily administration. Subjects were asked to complete 72 weeks of daily dosing.

Investigational medicinal product name

oral placebo

Investigational medicinal product code

ALZT-OP1b placebo

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ALZT-OP1b Placebo was supplied as an enterically coated tablet for once daily oral administration. Subjects were asked to complete 72 weeks of daily dosing.

Group 2

Arm description

ALZT-OP1 double active therapy (q.d. inhalation of active cromolyn via DPI + q.d. ibuprofen oral active tablet)

Arm type

Experimental

Investigational medicinal product name

cromolyn

Investigational medicinal product code

ALZT-OP1a

Other name

Pharmaceutical forms

Inhalation powder, hard capsule

Routes of administration

Inhalation use

Dosage and administration details

Investigational medicinal product name

ibuprofen

Investigational medicinal product code

ALZT-OP1b

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ALZT-OP1b (ibuprofen) was supplied as an enterically coated 10 mg tablet for once daily oral administration. Subjects were asked to complete 72 weeks of daily dosing

Group 3

Arm description

ALZT-OP1b (q.d. inhalation of placebo via DPI + q.d. oral active ibuprofen tablet)

Arm type

single active component - ibuprofen

Investigational medicinal product name

ibuprofen

Investigational medicinal product code

ALZT-OP1b

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ALZT-OP1b (ibuprofen) was supplied as an enterically coated 10 mg tablet for once daily oral administration. Subjects were asked to complete 72 weeks of daily dosing

Investigational medicinal product name

inhalation placebo

Investigational medicinal product code

ALZT-OP1a placebo

Other name

Pharmaceutical forms

Inhalation powder, hard capsule

Routes of administration

Inhalation use

Dosage and administration details

ALZT-OP1a Placebo was supplied as a powder blend encapsulated for once daily administration via oral inhalation using a mono-dose dry powder inhaler. Subjects were asked to complete 72 weeks of daily dosing.

Group 4

Arm description

q.d. inhalation of placebo via DPI + q.d. oral placebo tablet

Arm type

Placebo

Investigational medicinal product name

inhalation placebo

Investigational medicinal product code

ALZT-OP1a placebo

Other name

Pharmaceutical forms

Inhalation powder, hard capsule

Routes of administration

Inhalation use

Dosage and administration details

Investigational medicinal product name

oral placebo

Investigational medicinal product code

ALZT-OP1b placebo

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ALZT-OP1b Placebo was supplied as an enterically coated tablet for once daily oral administration. Subjects were asked to complete 72 weeks of daily dosing.

Number of subjects in period 1	Group 1	Group 2	Group 3	Group 4
Started	153	153	160	153
Completed	117	116	128	118
Not completed	36	37	32	35
Adverse event, serious fatal	3	1	2	-
Physician decision	-	-	-	1
Study terminated by Sponsor	1	-	1	-
Incorrect IP dispense	-	-	-	1
Abnormal lab results at baseline	-	-	-	1
Consent withdrawn by subject	16	20	15	19
Adverse event, non-fatal	7	5	6	5
Progressive Disease	-	-	1	1
Non-compliance with study drug	5	-	1	3
Site closed	-	1	-	1
Lost to follow-up	3	2	2	-
Lack of efficacy	1	1	1	3
Protocol deviation	-	7	3	-

Baseline characteristics

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Reporting group title

Group 1

Reporting group description

ALZT-OP1a (q.d. inhalation of active cromolyn via DPI + q.d. oral placebo tablet)

Reporting group title

Group 2

Reporting group description

ALZT-OP1 double active therapy (q.d. inhalation of active cromolyn via DPI + q.d. ibuprofen oral active tablet)

Reporting group title

Group 3

Reporting group description

ALZT-OP1b (q.d. inhalation of placebo via DPI + q.d. oral active ibuprofen tablet)

Reporting group title

Group 4

Reporting group description

q.d. inhalation of placebo via DPI + q.d. oral placebo tablet

Reporting group values	Group 1	Group 2	Group 3	Group 4	Total
Number of subjects	153	153	160	153	619
Age categorical
AZT-001 study participants were aged 55-79 years, inclusive.
Units: Subjects
Adults (18-64 years)	33	35	35	32	135
From 65-84 years	120	118	125	121	484
Gender categorical
Units: Subjects
Female	75	95	92	72	334
Male	78	58	68	81	285

Subject analysis set title

mITT

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

The mITT as a primary analysis set is defined as all randomized subjects who have a baseline CDR-SB as well as a CDR-SB post-baseline observation.

Subject analysis sets values	mITT
Number of subjects	594
Age categorical
AZT-001 study participants were aged 55-79 years, inclusive.
Units: Subjects
Adults (18-64 years)	125
From 65-84 years	469
Age continuous
Units:
	±
Gender categorical
Units: Subjects
Female	320
Male	274

End points

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Reporting group title

Group 1

Reporting group description

ALZT-OP1a (q.d. inhalation of active cromolyn via DPI + q.d. oral placebo tablet)

Reporting group title

Group 2

Reporting group description

ALZT-OP1 double active therapy (q.d. inhalation of active cromolyn via DPI + q.d. ibuprofen oral active tablet)

Reporting group title

Group 3

Reporting group description

ALZT-OP1b (q.d. inhalation of placebo via DPI + q.d. oral active ibuprofen tablet)

Reporting group title

Group 4

Reporting group description

q.d. inhalation of placebo via DPI + q.d. oral placebo tablet

Subject analysis set title

mITT

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

The mITT as a primary analysis set is defined as all randomized subjects who have a baseline CDR-SB as well as a CDR-SB post-baseline observation.

Primary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Primary contrast 1)

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End point title

Mean change from baseline to Week 72 in points scored on the CDR-SB (Primary contrast 1) ^[1]

End point description

Mean change from baseline to Week 72 in points scored on the CDR-SB for the following main contrast: - Group 2 (cromolyn active+Ibuprofen active) vs. Group 1 (cromolyn sodium active+Ibuprofen placebo)

End point type

Primary

End point timeframe

Baseline to Week 72

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: AZT-001 was designed as a factorial study in which the two primary contrasts consisted of comparing the combination treatment (Group 2; cromolyn + ibuprofen) compared to each of the single active component arms: Group 2 (combination) vs Group 1 (cromolyn active) and Group 2 (combination) vs Group 3 (ibuprofen active). A placebo arm (group 4) was included in the study. Secondary contrasts provided comparison of Group 2 (combination) vs Group 4 (placebo) and Group 1 (cromolyn active) vs Group 4.

End point values	Group 1	Group 2	mITT
Number of subjects analysed	147	145	292
Units: CDR-SB
least squares mean (confidence interval 95%)	2.17 (1.64 to 2.69)	2.33 (1.80 to 2.85)	0.16 (-0.58 to 0.90)

MMRM Analysis

Statistical analysis description

Results are based on a MMRM model including the fixed effects treatment, visit, treatment by visit interaction, region and the covariates APOe4, anti-dementia drug use, baseline CDR-SB and age assuming an unstructured correlation matrix.

Comparison groups

Group 1 v Group 2

Number of subjects included in analysis

292

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.675

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Variability estimate

Standard error of the mean

Primary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Primary contrast 2)

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End point title

Mean change from baseline to Week 72 in points scored on the CDR-SB (Primary contrast 2) ^[2]

End point description

Mean change from baseline to Week 72 in points scored on the CDR-SB for the following main contrast: - Group 2 (cromolyn active+Ibuprofen active) vs. Group 3 (cromolyn placebo+Ibuprofen active)

End point type

Primary

End point timeframe

Baseline to Week 72

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: AZT-001 was designed as a factorial study in which the two primary contrasts consisted of comparing the combination treatment (Group 2; cromolyn + ibuprofen) compared to each of the single active component arms: Group 2 (combination) vs Group 1 (cromolyn active) and Group 2 (combination) vs Group 3 (ibuprofen active). A placebo arm (group 4) was included in the study. Secondary contrasts provided comparison of Group 2 (combination) vs Group 4 (placebo) and Group 1 (cromolyn active) vs Group 4.

End point values	Group 2	Group 3	mITT
Number of subjects analysed	145	155	300
Units: CDR-SB
least squares mean (confidence interval 95%)	2.33 (1.80 to 2.85)	1.92 (1.42 to 2.43)	0.40 (-0.32 to 1.13)

MMRM Analysis

Statistical analysis description

Comparison groups

Group 2 v Group 3

Number of subjects included in analysis

300

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2764

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Variability estimate

Standard error of the mean

Secondary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Secondary contrast 1)

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End point title

Mean change from baseline to Week 72 in points scored on the CDR-SB (Secondary contrast 1) ^[3]

End point description

Mean change from baseline to Week 72 in points scored on the CDR-SB for the following secondary contrast: - Group 2 (cromolyn active+Ibuprofen active) vs. Group 4 (cromolyn placebo+Ibuprofen placebo);

End point type

Secondary

End point timeframe

Baseline to Week 72

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: AZT-001 was designed as a factorial study in which the two primary contrasts consisted of comparing the combination treatment (Group 2; cromolyn + ibuprofen) compared to each of the single active component arms: Group 2 (combination) vs Group 1 (cromolyn active) and Group 2 (combination) vs Group 3 (ibuprofen active). A placebo arm (group 4) was included in the study. Secondary contrasts provided comparison of Group 2 (combination) vs Group 4 (placebo) and Group 1 (cromolyn active) vs Group 4.

End point values	Group 2	Group 4	mITT
Number of subjects analysed	145	147	292
Units: CDR-SB
least squares mean (confidence interval 95%)	2.33 (1.80 to 2.85)	2.22 (1.70 to 2.74)	0.11 (-0.63 to 0.84)

MMRM Analysis

Statistical analysis description

Comparison groups

Group 2 v Group 4

Number of subjects included in analysis

292

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.776

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Variability estimate

Standard error of the mean

Secondary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Secondary contrast 2)

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End point title

Mean change from baseline to Week 72 in points scored on the CDR-SB (Secondary contrast 2) ^[4]

End point description

Mean change from baseline to Week 72 in points scored on the CDR-SB for the following secondary contrast: - Group 1 (cromolyn active+Ibuprofen placebo) vs. Group 4 (cromolyn sodium placebo+Ibuprofen placebo)

End point type

Secondary

End point timeframe

Baseline to Week 72

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: AZT-001 was designed as a factorial study in which the two primary contrasts consisted of comparing the combination treatment (Group 2; cromolyn + ibuprofen) compared to each of the single active component arms: Group 2 (combination) vs Group 1 (cromolyn active) and Group 2 (combination) vs Group 3 (ibuprofen active). A placebo arm (group 4) was included in the study. Secondary contrasts provided comparison of Group 2 (combination) vs Group 4 (placebo) and Group 1 (cromolyn active) vs Group 4.

End point values	Group 1	Group 4	mITT
Number of subjects analysed	147	147	294
Units: CDR-SB
least squares mean (confidence interval 95%)	2.17 (1.64 to 2.69)	2.22 (1.70 to 2.74)	-0.05 (-0.79 to 0.69)

MMRM Analysis

Statistical analysis description

Comparison groups

Group 1 v Group 4

Number of subjects included in analysis

294

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8912

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Variability estimate

Standard error of the mean

Adverse events

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Timeframe for reporting adverse events

3 September 2015 to 13 November 2020

Adverse event reporting additional description

Date of consent to last patient last visit.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

19.1E

Reporting group title

Group 1

Reporting group description

ALZT-OP1a (q.d. inhalation of active cromolyn via DPI + q.d. oral placebo tablet)

Reporting group title

Group 2

Reporting group description

ALZT-OP1 double active therapy (q.d. inhalation of active cromolyn via DPI + q.d. ibuprofen oral active tablet)

Reporting group title

Group 3

Reporting group description

ALZT-OP1b (q.d. inhalation of placebo via DPI + q.d. oral active ibuprofen tablet)

Reporting group title

Group 4

Reporting group description

q.d. inhalation of placebo via DPI + q.d. oral placebo tablet

Serious adverse events	Group 1	Group 2	Group 3	Group 4
Total subjects affected by serious adverse events
subjects affected / exposed	18 / 154 (11.69%)	15 / 153 (9.80%)	16 / 160 (10.00%)	15 / 152 (9.87%)
number of deaths (all causes)	6	2	3	3
number of deaths resulting from adverse events	6	2	3	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal stromal tumour
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metastases to bone
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metastatic uterine cancer
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Prostate cancer
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Arterial stenosis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Asthenia
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Death
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary infarction
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Pulmonary thrombosis
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Aggression
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Agitation
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anxiety
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Delusion
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Mental status changes
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	3 / 160 (1.88%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pubis fracture
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lumbar vertebral fracture
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Post lumbar puncture syndrome
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acetabulum fracture
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cervical vertebral fracture
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Concussion
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Head injury
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Traumatic intracranial haemorrhage
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Dolichocolon
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiac arrest
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 1
Atrial fibrillation
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	2 / 152 (1.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Bradycardia
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Sinus arrest
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Dementia
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	2 / 160 (1.25%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Cerebrovascular accident
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Dementia Alzheimer's type
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Cerebrospinal fluid leakage
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Encephalopathy
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Thrombotic stroke
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Deafness
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Rectal haemorrhage
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal ulcer haemorrhage
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Mesenteric vein thrombosis
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatic mass
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urethral stenosis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract obstruction
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Diabetic metabolic decompensation
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Osteoarthritis
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal instability
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ophthalmic herpes zoster
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia chlamydial
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia influenzal
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0.6%

Non-serious adverse events	Group 1	Group 2	Group 3	Group 4
Total subjects affected by non serious adverse events
subjects affected / exposed	76 / 154 (49.35%)	83 / 153 (54.25%)	79 / 160 (49.38%)	77 / 152 (50.66%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Basal cell carcinoma
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	2	1	0
Colon adenoma
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Endometrial cancer
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Haemangioma of skin
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Kidney angiomyolipoma
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Rectal adenoma
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Seborrhoeic keratosis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	3 / 160 (1.88%)	0 / 152 (0.00%)
occurrences all number	0	0	3	0
Skin papilloma
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Squamous cell carcinoma
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Squamous cell carcinoma of skin
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Vascular disorders
Aortic aneurysm
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	1	1	0
Aortic arteriosclerosis
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Circulatory collapse
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	1	0	0
Deep vein thrombosis
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Haematoma
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	2	0	0
Hypertension
subjects affected / exposed	3 / 154 (1.95%)	3 / 153 (1.96%)	2 / 160 (1.25%)	2 / 152 (1.32%)
occurrences all number	3	4	2	2
Hypotension
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	1	0	1
Iliac vein occlusion
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Thrombophlebitis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	2 / 152 (1.32%)
occurrences all number	0	0	0	2
Varicose ulceration
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Varicose vein
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Vena cava thrombosis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Surgical and medical procedures
Cardiac pacemaker insertion
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Cataract operation
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	1	2	1	0
Cyst removal
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Hip surgery
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Intraocular lens implant
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	2
Myringotomy
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Nephrectomy
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Shoulder arthroplasty
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Skin lesion excision
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Skin neoplasm excision
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Tooth extraction
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	1	0	1	0
Uterine dilation and curettage
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
General disorders and administration site conditions
Condition aggravated
subjects affected / exposed	6 / 154 (3.90%)	10 / 153 (6.54%)	9 / 160 (5.63%)	5 / 152 (3.29%)
occurrences all number	8	12	11	6
Asthenia
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	0	0	1	1
Chest discomfort
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Chest pain
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	1	0	1	1
Fatigue
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	1	1	1	1
Feeling abnormal
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Gait disturbance
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	2	1	0
Influenza like illness
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Malaise
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Multiple organ dysfunction syndrome
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Oedema peripheral
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	2 / 160 (1.25%)	4 / 152 (2.63%)
occurrences all number	0	1	2	5
Pain
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Peripheral swelling
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Puncture site pain
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	2	1	0
Pyrexia
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	1	0	0	1
Ulcer
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	2 / 160 (1.25%)	0 / 152 (0.00%)
occurrences all number	0	0	4	0
Hypersensitivity
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Multiple allergies
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	2 / 154 (1.30%)	1 / 153 (0.65%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	2	1	0	1
Testicular pain
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Uterine cyst
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	7 / 154 (4.55%)	7 / 153 (4.58%)	5 / 160 (3.13%)	7 / 152 (4.61%)
occurrences all number	7	7	5	7
Asthma
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Bronchitis chronic
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Epistaxis
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	1	0	2
Dry throat
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Dyspnoea
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Increased upper airway secretion
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Nasal congestion
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Oropharyngeal pain
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	1	1	1	0
Productive cough
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Pulmonary mass
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Rales
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	2	0	0
Rhinitis allergic
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Rhinorrhoea
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	3	0	1	0
Sinus congestion
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	2	0	0
Sleep apnoea syndrome
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	3	0	0
Suffocation feeling
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Throat irritation
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	1	1	0
Upper respiratory tract inflammation
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Wheezing
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	2	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	2 / 154 (1.30%)	5 / 153 (3.27%)	8 / 160 (5.00%)	6 / 152 (3.95%)
occurrences all number	2	5	10	7
Abnormal dreams
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	1	0	1	0
Adjustment disorder with depressed mood
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Aggression
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Agitation
subjects affected / exposed	1 / 154 (0.65%)	2 / 153 (1.31%)	1 / 160 (0.63%)	2 / 152 (1.32%)
occurrences all number	2	2	1	2
Confusional state
subjects affected / exposed	2 / 154 (1.30%)	2 / 153 (1.31%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	2	2	1	0
Delirium
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	2
Delusion
subjects affected / exposed	0 / 154 (0.00%)	3 / 153 (1.96%)	2 / 160 (1.25%)	0 / 152 (0.00%)
occurrences all number	0	4	2	0
Delusion of replacement
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Delusional disorder, unspecified type
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Depressed mood
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	2	0	0	1
Depression
subjects affected / exposed	2 / 154 (1.30%)	2 / 153 (1.31%)	4 / 160 (2.50%)	3 / 152 (1.97%)
occurrences all number	2	2	4	3
Depressive symptom
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Dermatillomania
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Disorientation
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Hallucination
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	1	1	1	0
Hallucination, visual
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	2	0	0	0
Illusion
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Insomnia
subjects affected / exposed	2 / 154 (1.30%)	3 / 153 (1.96%)	4 / 160 (2.50%)	3 / 152 (1.97%)
occurrences all number	2	3	4	3
Irritability
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	2	0	0	0
Mood swings
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Nervousness
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Nightmare
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	0	1	1	1
Paranoia
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Persistent depressive disorder
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Rapid eye movement sleep behaviour disorder
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	2	0	0	0
Restlessness
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Sleep disorder
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	2 / 160 (1.25%)	0 / 152 (0.00%)
occurrences all number	0	1	2	0
Aortic bruit
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	2 / 160 (1.25%)	0 / 152 (0.00%)
occurrences all number	0	1	2	0
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	2	0	1
Blood bilirubin increased
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Blood cholesterol increased
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	2	0	0
Blood creatinine increased
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	0	0	1	1
Blood glucose decreased
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	1	0	0	1
Blood glucose increased
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Blood potassium increased
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	1	0	0	1
Blood pressure increased
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Blood testosterone decreased
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	2	0	0
Blood urine present
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Breath sounds abnormal
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Cardiac murmur
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Coronavirus test positive
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
C-reactive protein increased
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Electrocardiogram QT prolonged
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	0 / 160 (0.00%)	4 / 152 (2.63%)
occurrences all number	2	0	0	4
Electrocardiogram T wave inversion
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Electrocardiogram P wave abnormal
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Glucose urine present
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Haematocrit decreased
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	1	0	0
Haemoglobin decreased
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	1	0	0
Heart rate irregular
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Hepatic enzyme increased
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	0	0	1	1
Liver function test abnormal
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Liver function test increased
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Mean cell haemoglobin concentration decreased
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Mean cell haemoglobin decreased
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Mean cell haemoglobin increased
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Mean cell volume decreased
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Mean cell volume increased
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Prostatic specific antigen increased
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Protein urine present
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Pupillary light reflex tests abnormal
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
QRS axis abnormal
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	2	0
Red blood cell sedimentation rate increased
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Red blood cells urine positive
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	2 / 152 (1.32%)
occurrences all number	0	0	0	2
Red cell distribution width increased
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Reticulocyte count decreased
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Reticulocyte count increased
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	1	0	1
Smear cervix abnormal
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Urine analysis abnormal
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Urine leukocyte esterase positive
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Weight decreased
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	2 / 160 (1.25%)	0 / 152 (0.00%)
occurrences all number	0	0	2	0
White blood cell count increased
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
White blood cells urine positive
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	5 / 154 (3.25%)	4 / 153 (2.61%)	7 / 160 (4.38%)	4 / 152 (2.63%)
occurrences all number	5	4	7	5
Contusion
subjects affected / exposed	5 / 154 (3.25%)	2 / 153 (1.31%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	5	2	0	1
Accidental overdose
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Alcohol poisoning
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Animal bite
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Arthropod bite
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	2 / 160 (1.25%)	0 / 152 (0.00%)
occurrences all number	1	1	2	0
Arthropod sting
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Burns first degree
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Burns second degree
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Exposure to toxic agent
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Foot fracture
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	1	0	0	1
Ear injury
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Eyelid injury
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Hand fracture
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	1	0	0	1
Head injury
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	1	0	1	0
Humerus fracture
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	2 / 160 (1.25%)	0 / 152 (0.00%)
occurrences all number	0	1	2	0
Incorrect route of drug administration
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	1	1	1	1
Infusion related reaction
Additional description: Infusion Reaction to carboplatin infusion for cancer treatment.
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Injury
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Laceration
subjects affected / exposed	2 / 154 (1.30%)	2 / 153 (1.31%)	2 / 160 (1.25%)	1 / 152 (0.66%)
occurrences all number	3	2	2	1
Ligament sprain
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Limb injury
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Mouth injury
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Muscle strain
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	3 / 152 (1.97%)
occurrences all number	0	0	1	3
Post lumbar puncture syndrome
subjects affected / exposed	3 / 154 (1.95%)	1 / 153 (0.65%)	2 / 160 (1.25%)	3 / 152 (1.97%)
occurrences all number	3	1	2	3
Procedural pain
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	1	1	0
Pubis fracture
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Radius fracture
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Road traffic accident
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Scratch
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Skin abrasion
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	1	1	0
Subdural haematoma
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Traumatic haemorrhage
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Upper limb fracture
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Wrist fracture
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Congenital, familial and genetic disorders
Hydrocele
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Atrial fibrillation
subjects affected / exposed	1 / 154 (0.65%)	2 / 153 (1.31%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	1	2	1	0
Atrioventricular block first degree
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Atrioventricular block second degree
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	2 / 152 (1.32%)
occurrences all number	0	0	0	2
Bradycardia
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	0	0	1	1
Cardiogenic shock
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Sinus bradycardia
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	2	0	0
Sinus node dysfunction
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Supraventricular tachycardia
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Tachyarrhythmia
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Ventricular extrasystoles
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Nervous system disorders
Dementia Alzheimer's type
subjects affected / exposed	9 / 154 (5.84%)	9 / 153 (5.88%)	8 / 160 (5.00%)	5 / 152 (3.29%)
occurrences all number	9	10	8	5
Headache
subjects affected / exposed	7 / 154 (4.55%)	5 / 153 (3.27%)	10 / 160 (6.25%)	4 / 152 (2.63%)
occurrences all number	7	5	11	4
Dizziness
subjects affected / exposed	0 / 154 (0.00%)	5 / 153 (3.27%)	7 / 160 (4.38%)	3 / 152 (1.97%)
occurrences all number	0	6	8	3
Cognitive disorder
subjects affected / exposed	5 / 154 (3.25%)	3 / 153 (1.96%)	1 / 160 (0.63%)	5 / 152 (3.29%)
occurrences all number	6	3	1	5
Amputation stump pain
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Aphasia
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	2 / 160 (1.25%)	1 / 152 (0.66%)
occurrences all number	1	0	2	1
Balance disorder
subjects affected / exposed	2 / 154 (1.30%)	2 / 153 (1.31%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	2	2	1	1
Carpal tunnel syndrome
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Dementia
subjects affected / exposed	0 / 154 (0.00%)	3 / 153 (1.96%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	4	0	0
Dementia with Lewy bodies
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Diabetic neuropathy
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	1	0	1	0
Gait apraxia
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	2	0
Hypersomnia
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Hyposmia
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Ischaemic stroke
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Memory impairment
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	2	0	1
Nerve compression
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Nystagmus
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Occipital neuralgia
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	1	1	0
Paraesthesia
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	2	1	0
Parkinsonian rest tremor
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Parkinsonism
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	2	0	0	1
Presyncope
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	1	0	0	1
Sciatica
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Somnolence
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	2 / 152 (1.32%)
occurrences all number	1	0	0	2
Syncope
subjects affected / exposed	0 / 154 (0.00%)	3 / 153 (1.96%)	2 / 160 (1.25%)	1 / 152 (0.66%)
occurrences all number	0	3	3	1
Tardive dyskinesia
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Transient global amnesia
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Tremor
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	2	0	1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	3 / 154 (1.95%)	3 / 153 (1.96%)	3 / 160 (1.88%)	1 / 152 (0.66%)
occurrences all number	3	3	3	1
Leukocytosis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	2 / 160 (1.25%)	0 / 152 (0.00%)
occurrences all number	0	0	2	0
Microcytic anaemia
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Normochromic normocytic anaemia
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	2 / 152 (1.32%)
occurrences all number	0	1	0	2
White blood cell disorder
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Ear and labyrinth disorders
Cerumen impaction
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Deafness bilateral
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Deafness unilateral
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Sudden hearing loss
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Tinnitus
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Vertigo
subjects affected / exposed	3 / 154 (1.95%)	1 / 153 (0.65%)	2 / 160 (1.25%)	0 / 152 (0.00%)
occurrences all number	3	1	2	0
Eye disorders
Blepharitis
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	1	0	0	1
Cataract
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	2	0	0
Conjunctival haemorrhage
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Dry eye
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Eye irritation
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Glaucoma
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	1	1	1	0
Lacrimation increased
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Miosis
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	1	1	0
Retinal detachment
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Visual acuity reduced
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	3 / 160 (1.88%)	5 / 152 (3.29%)
occurrences all number	0	1	3	5
Abdominal discomfort
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	2 / 160 (1.25%)	0 / 152 (0.00%)
occurrences all number	0	1	3	0
Abdominal pain
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	1 / 160 (0.63%)	2 / 152 (1.32%)
occurrences all number	1	1	1	2
Abdominal pain lower
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Abdominal pain upper
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	2 / 160 (1.25%)	0 / 152 (0.00%)
occurrences all number	0	1	2	0
Anal incontinence
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	1	0	1	0
Cheilitis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Coeliac disease
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Constipation
subjects affected / exposed	2 / 154 (1.30%)	1 / 153 (0.65%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	2	1	1	1
Eructation
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Diverticulum
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	1	1	0
Diverticulum intestinal
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Dysphagia
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Faecal incontinence
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Faeces hard
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Flatulence
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Gastric ulcer
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Gastritis
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	1	1	0
Gastrointestinal sounds abnormal
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	1	1	1	0
Haemorrhoids
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	2	0	1	0
Hiatus hernia
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Inguinal hernia
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	2	0	1	0
Irritable bowel syndrome
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Large intestine polyp
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	2	0	1	1
Nausea
subjects affected / exposed	4 / 154 (2.60%)	1 / 153 (0.65%)	2 / 160 (1.25%)	2 / 152 (1.32%)
occurrences all number	4	1	2	2
Oesophagitis
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Peptic ulcer
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Rectal haemorrhage
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Salivary gland disorder
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Tooth impacted
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Toothache
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	1	1	0
Vomiting
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	1 / 160 (0.63%)	3 / 152 (1.97%)
occurrences all number	0	2	1	3
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	2	0
Cholelithiasis
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	2	0	0
Hepatic cyst
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Cutis laxa
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Decubitus ulcer
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Dermatitis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Dermatitis contact
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	1	0	0
Diabetic foot
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Eczema
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	1	1	0
Erythema
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Haemorrhage subcutaneous
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Hyperkeratosis
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	2	0	0	0
Hypertrichosis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Miliaria
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Papule
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Petechiae
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Photodermatosis
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Pruritus
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	2 / 160 (1.25%)	1 / 152 (0.66%)
occurrences all number	0	2	2	1
Rash
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	2 / 160 (1.25%)	2 / 152 (1.32%)
occurrences all number	2	0	2	2
Rash pruritic
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Scab
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Seborrhoeic dermatitis
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Skin lesion
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	0	0	1	1
Telangiectasia
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Urticaria
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	1	0	0	2
Urticaria chronic
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Xanthelasma
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Chronic kidney disease
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	2 / 152 (1.32%)
occurrences all number	0	0	0	2
Haematuria
subjects affected / exposed	1 / 154 (0.65%)	2 / 153 (1.31%)	2 / 160 (1.25%)	3 / 152 (1.97%)
occurrences all number	1	2	2	3
Hydronephrosis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Hypertonic bladder
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	2	1	0
Incontinence
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Leukocyturia
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Nephrolithiasis
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Pollakiuria
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	0	0	1	1
Renal cyst
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Ureterolithiasis
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	1	0	0
Urinary incontinence
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	1	1	1	1
Urinary retention
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	1	0	0	1
Urinary tract inflammation
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	1	0	0
Endocrine disorders
Endocrine disorders
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Hypothyroidism
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	3 / 160 (1.88%)	1 / 152 (0.66%)
occurrences all number	2	0	3	1
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	5 / 154 (3.25%)	1 / 153 (0.65%)	3 / 160 (1.88%)	3 / 152 (1.97%)
occurrences all number	5	1	3	4
Arthralgia
subjects affected / exposed	4 / 154 (2.60%)	1 / 153 (0.65%)	3 / 160 (1.88%)	2 / 152 (1.32%)
occurrences all number	5	1	5	2
Arthritis
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	2	1	0
Fracture pain
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Facial asymmetry
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Muscle spasms
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Muscular weakness
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	2	0	0	0
Musculoskeletal discomfort
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	2 / 160 (1.25%)	0 / 152 (0.00%)
occurrences all number	0	0	2	0
Musculoskeletal pain
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	2	0	1	1
Myalgia
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Neck pain
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	2 / 160 (1.25%)	1 / 152 (0.66%)
occurrences all number	1	0	2	1
Osteoarthritis
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	2 / 160 (1.25%)	1 / 152 (0.66%)
occurrences all number	0	1	2	1
Osteopenia
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Osteoporosis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Pain in extremity
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	1	1	0
Plantar fasciitis
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Rotator cuff syndrome
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	2	0	0
Soft tissue mass
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Spinal deformity
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Spinal instability
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Spinal osteoarthritis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	2 / 160 (1.25%)	0 / 152 (0.00%)
occurrences all number	0	0	2	0
Spinal pain
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	2 / 160 (1.25%)	1 / 152 (0.66%)
occurrences all number	0	0	2	1
Tendonitis
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	1	0	1	1
Tenosynovitis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	2	0
Infections and infestations
Urinary tract infection
subjects affected / exposed	7 / 154 (4.55%)	7 / 153 (4.58%)	12 / 160 (7.50%)	5 / 152 (3.29%)
occurrences all number	8	8	13	6
Upper respiratory tract infection
subjects affected / exposed	7 / 154 (4.55%)	10 / 153 (6.54%)	6 / 160 (3.75%)	2 / 152 (1.32%)
occurrences all number	7	12	6	2
Nasopharyngitis
subjects affected / exposed	1 / 154 (0.65%)	3 / 153 (1.96%)	6 / 160 (3.75%)	3 / 152 (1.97%)
occurrences all number	1	3	8	3
Acute sinusitis
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Borrelia infection
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Bronchitis
subjects affected / exposed	4 / 154 (2.60%)	4 / 153 (2.61%)	0 / 160 (0.00%)	2 / 152 (1.32%)
occurrences all number	4	4	0	2
Bronchitis viral
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Cellulitis
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	2 / 160 (1.25%)	0 / 152 (0.00%)
occurrences all number	1	1	2	0
Clostridium difficile colitis
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Clostridium difficile infection
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Conjunctivitis
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Cystitis
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Fungal skin infection
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	2 / 160 (1.25%)	1 / 152 (0.66%)
occurrences all number	2	0	2	1
Diverticulitis
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	1	1	0
Gastroenteritis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Gastroenteritis viral
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Gingival abscess
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Gingivitis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Herpes simplex
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	1	0	0
Herpes virus infection
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Herpes zoster
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	1	0	1	1
Influenza
subjects affected / exposed	2 / 154 (1.30%)	2 / 153 (1.31%)	2 / 160 (1.25%)	0 / 152 (0.00%)
occurrences all number	2	2	2	0
Localised infection
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Onychomycosis
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	1	1	0
Oral candidiasis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Oral herpes
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Otitis externa
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0	0
Otitis media acute
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Otitis media chronic
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Periodontitis
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Pharyngitis
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	1	0	0	1
Pneumonia
subjects affected / exposed	0 / 154 (0.00%)	3 / 153 (1.96%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	0	3	1	1
Respiratory tract infection
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Rhinitis
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	1	0	1	0
Sinusitis
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	2 / 160 (1.25%)	1 / 152 (0.66%)
occurrences all number	1	0	2	1
Tooth abscess
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	1	0	1
Tooth infection
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	1	0	0	1
Vaginal infection
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	1	0	1
Viral infection
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	2 / 160 (1.25%)	1 / 152 (0.66%)
occurrences all number	0	0	3	1
Viral upper respiratory tract infection
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	1	1	1	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Dehydration
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	1	1	0	1
Diabetes mellitus
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	1	1	1	1
Diabetes mellitus inadequate control
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	0	0	1	1
Diabetic metabolic decompensation
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Gout
subjects affected / exposed	1 / 154 (0.65%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	1	0	0	1
Hypercholesterolaemia
subjects affected / exposed	1 / 154 (0.65%)	1 / 153 (0.65%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	1	1	1	1
Hyperglycaemia
subjects affected / exposed	2 / 154 (1.30%)	0 / 153 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	2	0	0	0
Hyperkalaemia
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Hyperlipidaemia
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	0	1	0	0
Hypoglycaemia
subjects affected / exposed	0 / 154 (0.00%)	1 / 153 (0.65%)	1 / 160 (0.63%)	1 / 152 (0.66%)
occurrences all number	0	1	1	1
Hypokalaemia
subjects affected / exposed	0 / 154 (0.00%)	2 / 153 (1.31%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	2	0	1
Hypomagnesaemia
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	0	1
Hyponatraemia
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0
Polydipsia
subjects affected / exposed	0 / 154 (0.00%)	0 / 153 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	0	0	1	0

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results:
A phase III Safety and Efficacy Study of ALZT-OP1 in Subjects with Evidence of Early Alzheimer’s Disease.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Primary contrast 1)

Primary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Primary contrast 1)

Primary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Primary contrast 2)

Primary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Primary contrast 2)

Secondary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Secondary contrast 1)

Secondary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Secondary contrast 1)

Secondary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Secondary contrast 2)

Secondary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Secondary contrast 2)

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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

Clinical trials

Clinical Trial Results: A phase III Safety and Efficacy Study of ALZT-OP1 in Subjects with Evidence of Early Alzheimer’s Disease.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Primary contrast 1)

Primary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Primary contrast 1)

Primary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Primary contrast 2)

Primary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Primary contrast 2)

Secondary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Secondary contrast 1)

Secondary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Secondary contrast 1)

Secondary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Secondary contrast 2)

Secondary: Mean change from baseline to Week 72 in points scored on the CDR-SB (Secondary contrast 2)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A phase III Safety and Efficacy Study of ALZT-OP1 in Subjects with Evidence of Early Alzheimer’s Disease.