Download PDF

Clinical Trial Results:
Optimal Treatment of Drug Resistant Hypertension

Summary
EudraCT number	2008-007149-30
Trial protocol	GB
Global end of trial date	26 Jun 2015

Results information
Results version number	v1(current)
This version publication date	21 Feb 2020
First version publication date	21 Feb 2020
Other versions
Summary report(s)	Pathway 2 Publication

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

Pathway 2

ISRCTN number

US NCT number

NCT02369081

WHO universal trial number (UTN)

Sponsor organisation name

Cambridge University Hospitals NHS Foundation Trust & the University of Cambridge

Sponsor organisation address

R&D Department, Addenbrooke's Hospital, Hills Road, Cambridge, United Kingdom, CB2 0QQ

Public contact

Morris J Brown, William Harvey Research Institute, Queen Mary University of London, morris.brown@qmul.ac.uk

Scientific contact

Morris J Brown, William Harvey Research Institute, Queen Mary University of London, morris.brown@qmul.ac.uk

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

04 Jan 2016

Is this the analysis of the primary completion data?

Yes

Primary completion date

25 Jun 2015

Global end of trial reached?

Yes

Global end of trial date

26 Jun 2015

Was the trial ended prematurely?

Main objective of the trial

The primary objective is to test our primary hypothesis which states that the commonest cause of resistant hypertension is excessive sodium retention, and that further diuretic therapy, i.e. spironolactone will be superior to other potential "add-on drugs" for people with inadequate blood pressure control despite treatment with three drugs, i.e. Ace Inhibitors, Calcium Channel Blockers and Diuretics (A+C+D).

Protection of trial subjects

Serious Adverse Events were documented and reported to the Chief Investigator and to regulatory authorities, in accordance with local an national requirements. The study was approved by Cambridgeshire Research Ethics Committee and all participants gave written informed consent. A Study Steering Committee was responsible for evaluating and reporting the results of the trial.

Background therapy

Evidence for comparator

Actual start date of recruitment

15 May 2009

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 348

Worldwide total number of subjects

348

EEA total number of subjects

348

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)

204

From 65 to 84 years

144

85 years and over

Subject disposition

Top of page

Recruitment details

Between May 15, 2009, and July 8, 2004, we screened 436 patients from 12 secondary and two primary sites in the UK for this 12-month randomized crossover trial

Screening details

We screened 436 and enrolled 335 patients aged 18-79 with seated CSBP ≥140 mm Hg (or ≥135 mm Hg in case of diabetics) and HSBP (18 readings over 4 days) ≥130 mm Hg, despite treatment for at least 3 months with maximally tolerated doses of three drugs.

Number of subjects started

436 ^[1]

Number of subjects completed

335 ^[2]

Reason: Number of subjects

not eligible: 88

Reason: Number of subjects

did not take study drug: 13

Notes
[1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: 88 patients were excluded as not eligible ,13 did not take study drug
[2] - The number of subjects reported to be in the pre-assignment period is not consistent with the number starting period 1. It is expected that the number completing the pre-assignment period are also present in the arms in period 1.
Justification: 88 patients were excluded as not eligible ,13 did not take study drug

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

Blinding implementation details

Patients rotated through 4 cycles of: 1) spironolactone 25-50 mg, 2) doxazosin 4-8 mg, 3) bisoprolol 5-10 mg, and 4) placebo. The complete set of permutations of the sequence order for the treatments were randomly ordered using computer generated pseudo random numbers. Study sites received the allocations for participants via a web-based randomization system. The study drugs were masked by re-encapsulation. Investigators/patients were masked to the identity of drugs, and to their sequence alloca

Are arms mutually exclusive

Spironolactone

Arm description

Patients received spironolactone 25 mg for weeks 0-6. The dose was doubled in weeks 6-12

Arm type

Experimental

Investigational medicinal product name

Spironolactone

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

12 weeks of oral treatment with 25-50 g of spironolactone, in addition to their baseline blood pressure drugs. The dose was doubled after 6 weeks.

doxazosin

Arm description

Arm type

Experimental

Investigational medicinal product name

doxazosin

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

12 weeks of once treatment with 4-8 g of doxazosin, in addition to their baseline blood pressure drugs. The dose was doubled after 6 weeks.

bisoprolol

Arm description

Arm type

Experimental

Investigational medicinal product name

bisoprolol

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

12 weeks of once treatment with 5-10 g of bisoprolol, in addition to their baseline blood pressure drugs. The dose was doubled after 6 weeks.

placebo

Arm description

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

placebo

Number of subjects in period 1	Spironolactone	doxazosin	bisoprolol	placebo
Started	285	282	285	274
Completed	267	264	268	264
Not completed	18	18	17	10
Adverse event, serious fatal	-	1	-	-
subject unwilling to continue	3	-	-	-
Adverse event, non-fatal	4	8	4	3
patient unwilling to continue	-	5	6	1
investigator terminated participation	6	1	2	1
Lost to follow-up	1	-	1	-
non-compliance	1	-	-	-
other reason	3	2	4	4
Protocol deviation	-	1	-	1

Baseline characteristics

Top of page

Reporting group title

Overall trial

Reporting group description

Notes
[1] - The number of subjects reported to be in the baseline period is not equal to the worldwide number of subjects enrolled in the trial. It is expected that these numbers will be the same.
Justification: 88 patients were excluded as not eligible ,13 did not take study drug

Reporting group values	Overall trial	Total
Number of subjects	335	335
Age categorical
Units: Subjects
In utero		0
Preterm newborn infants (gestational age < 37 wks)		0
Newborns (0-27 days)		0
Infants and toddlers (28 days-23 months)		0
Children (2-11 years)		0
Adolescents (12-17 years)		0
Adults (18-64 years)		0
From 65-84 years		0
85 years and over		0
Age continuous
Units: years
arithmetic mean (standard deviation)	61.4 ( 9.6 )	-
Gender categorical
Units: Subjects
Female	105	105
Male	230	230

End points

Top of page

Reporting group title

Spironolactone

Reporting group description

Patients received spironolactone 25 mg for weeks 0-6. The dose was doubled in weeks 6-12

Reporting group title

doxazosin

Reporting group description

Reporting group title

bisoprolol

Reporting group description

Reporting group title

placebo

Reporting group description

Primary: home systolic blood pressure

Top of page

End point title

home systolic blood pressure

End point description

recorded in the morning and the evening in triplicate, on 4 consecutive days before study visit. A maximum of the last 18 recordings for each measurement period -ie days 2-4 if all completed. A minimum of 6 blood pressure recordings per measurement period was reuqired for a valid measurement.

End point type

Primary

End point timeframe

measured throughout the treatment cycle at week 6 and week 12

End point values	Spironolactone	doxazosin	bisoprolol	placebo
Number of subjects analysed	285	282	285	274
Units: mmHg
least squares mean (confidence interval 95%)	134.9 (134.0 to 135.9)	139.0 (138.0 to 140.0)	139.4 (138.4 to 140.4)	143.6 (142.6 to 144.6)

Spironalactone vs placebo

Statistical analysis description

This is the first analysis in a hierarchy whereby a comparison was made if, and only if, all the preceding comparisons were statistically significant

Comparison groups

Spironolactone v placebo

Number of subjects included in analysis

559

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-8.7

Confidence interval

level

95%

sides

2-sided

lower limit

-9.72

upper limit

-7.69

Notes
[1] - This is a cross-over study, so the number of subjects is incorrect, but cannot be edited

Spironalactone vs mean bisoprolol and doxazosin

Statistical analysis description

This is the second analysis in a hierarchy whereby a comparison was made if, and only if, all the preceding comparisons were statistically significant

Comparison groups

Spironolactone v doxazosin v bisoprolol

Number of subjects included in analysis

852

Analysis specification

Pre-specified

Analysis type

superiority ^[2]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-4.26

Confidence interval

level

95%

sides

2-sided

lower limit

-5.13

upper limit

-3.38

Notes
[2] - this is a cross-over study so the number of subjects is incorrect, but cannot be edited

Spironalactone vs doxazosin

Statistical analysis description

This is the third analysis in a hierarchy whereby a comparison was made if, and only if, all the preceding comparisons were statistically significant

Comparison groups

Spironolactone v doxazosin

Number of subjects included in analysis

567

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-4.03

Confidence interval

level

95%

sides

2-sided

lower limit

-5.04

upper limit

-3.02

Notes
[3] - This is a cross-over study so the number of subjects is incorrect, but cannot be edited

Spironalactone vs bisaprolol

Statistical analysis description

This is the fourth analysis in a hierarchy whereby a comparison was made if, and only if, all the preceding comparisons were statistically significant

Comparison groups

Spironolactone v bisoprolol

Number of subjects included in analysis

570

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

< 0.0001

Method

Mixed models analysis

Parameter type

Mean difference (net)

Point estimate

-4.48

Confidence interval

level

95%

sides

2-sided

lower limit

-5.5

upper limit

-3.46

Notes
[4] - this is a cross over study so the number of subjects is incorrect but cannot be edited

Adverse events

Top of page

Timeframe for reporting adverse events

Timeframe for AE

Adverse event reporting additional description

AE additional description

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

19.0

Reporting group title

spironolactone

Reporting group description

Reporting group title

doxazosin

Reporting group description

Reporting group title

placebo

Reporting group description

Reporting group title

bisoprolol

Reporting group description

Serious adverse events	spironolactone	doxazosin	placebo	bisoprolol
Total subjects affected by serious adverse events
subjects affected / exposed	6 / 285 (2.11%)	4 / 282 (1.42%)	5 / 274 (1.82%)	7 / 285 (2.46%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma
Additional description: Bladder transitional cell carcinoma
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (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
Squamous cell carcinoma
Additional description: Squamous cell carcinoma
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (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
Vascular disorders
Hypertension
Additional description: Hypertension
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
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
Surgical and medical procedures
Cardiac pacemaker insertion
Additional description: Cardiac pacemaker insertion
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
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
Hernia repair
Additional description: Hernia repair
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (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
Skin graft
Additional description: Skin graft
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (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
General disorders and administration site conditions
Chest pain
Additional description: Chest pain
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
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
Fatigue
Additional description: Fatigue
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
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
Gait disturbance
Additional description: Gait disturbance
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (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
Malaise
Additional description: Malaise
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
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
Respiratory, thoracic and mediastinal disorders
Cough
Additional description: Cough
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
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
Dyspnoea exertional
Additional description: Dyspnoea exertional
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary oedema
Additional description: Pulmonary oedema
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (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
Wheezing
Additional description: Wheezing
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ankle fracture
Additional description: Ankle fracture
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
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 disorders
Atrial fibrillation
Additional description: Atrial fibrillation
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (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
Bradycardia
Additional description: Bradycardia
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
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
Palpitations
Additional description: Palpitations
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (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
Sick sinus syndrome
Additional description: Sick sinus syndrome
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
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
Supraventricular tachycardia
Additional description: Supraventricular tachycardia
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (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
Nervous system disorders
Diabetic neuropathy
Additional description: Diabetic neuropathy
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
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
Dizziness
Additional description: Dizziness
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
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
Transient ischaemic attack
Additional description: Transient ischaemic attack
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
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
Eye disorders
Retinal haemorrhage
Additional description: Retinal haemorrhage
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (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
Abdominal distension
Additional description: Abdominal distension
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
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
Gastrooesophageal reflux disease
Additional description: Gastrooesophageal reflux disease
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (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
Nausea
Additional description: Nausea
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
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
Skin and subcutaneous tissue disorders
Skin ulcer
Additional description: Skin ulcer
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (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
Renal and urinary disorders
Calculus ureteric
Additional description: Calculus ureteric
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
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
Musculoskeletal and connective tissue disorders
Back pain
Additional description: Back pain
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (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
Infections and infestations
Escherichia sepsis
Additional description: Escherichia sepsis
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (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
Metabolism and nutrition disorders
Hyperkalaemia
Additional description: Hyperkalaemia
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (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
Type 2 diabetes mellitus
Additional description: Type 2 diabetes mellitus
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	spironolactone	doxazosin	placebo	bisoprolol
Total subjects affected by non serious adverse events
subjects affected / exposed	168 / 285 (58.95%)	173 / 282 (61.35%)	134 / 274 (48.91%)	180 / 285 (63.16%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
Additional description: Melanocytic naevus
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Thyroid neoplasm
Additional description: Thyroid neoplasm
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Vascular disorders
Aortic aneurysm
Additional description: Aortic aneurysm
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Flushing
Additional description: Flushing
subjects affected / exposed	2 / 285 (0.70%)	2 / 282 (0.71%)	0 / 274 (0.00%)	2 / 285 (0.70%)
occurrences all number	2	2	0	2
Hypotension
Additional description: Hypotension
subjects affected / exposed	0 / 285 (0.00%)	5 / 282 (1.77%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	5	0	1
Lymphoedema
Additional description: Lymphoedema
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Orthostatic hypotension
Additional description: Orthostatic hypotension
subjects affected / exposed	0 / 285 (0.00%)	2 / 282 (0.71%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	2	0	1
Peripheral coldness
Additional description: Peripheral coldness
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	2 / 285 (0.70%)
occurrences all number	0	0	0	2
Thrombophlebitis superficial
Additional description: Thrombophlebitis superficial
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Surgical and medical procedures
Cataract operation
Additional description: Cataract operation
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	1	0	0	1
Cyst removal
Additional description: Cyst removal
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Endodontic procedure
Additional description: Endodontic procedure
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Mole excision
Additional description: Mole excision
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Orthopedic procedure
Additional description: Orthopedic procedure
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Skin neoplasm excision
Additional description: Skin neoplasm excision
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Tooth extraction
Additional description: Tooth extraction
subjects affected / exposed	1 / 285 (0.35%)	1 / 282 (0.35%)	0 / 274 (0.00%)	2 / 285 (0.70%)
occurrences all number	1	1	0	2
Tooth repair
Additional description: Tooth repair
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
General disorders and administration site conditions
Asthenia
Additional description: Asthenia
subjects affected / exposed	3 / 285 (1.05%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	4	0	0	1
Chest discomfort
Additional description: Chest discomfort
subjects affected / exposed	2 / 285 (0.70%)	3 / 282 (1.06%)	0 / 274 (0.00%)	5 / 285 (1.75%)
occurrences all number	2	3	0	5
Chest pain
Additional description: Chest pain
subjects affected / exposed	1 / 285 (0.35%)	4 / 282 (1.42%)	1 / 274 (0.36%)	2 / 285 (0.70%)
occurrences all number	1	4	1	2
Cyst
Additional description: Cyst
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Discomfort
Additional description: Discomfort
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Drug intolerance
Additional description: Drug intolerance
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Exercise tolerance decreased
Additional description: Exercise tolerance decreased
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Fatigue
Additional description: Fatigue
subjects affected / exposed	9 / 285 (3.16%)	19 / 282 (6.74%)	9 / 274 (3.28%)	22 / 285 (7.72%)
occurrences all number	9	19	10	23
Feeling abnormal
Additional description: Feeling abnormal
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	1 / 274 (0.36%)	1 / 285 (0.35%)
occurrences all number	1	0	1	1
Gait disturbance
Additional description: Gait disturbance
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Influenza like illness
Additional description: Influenza like illness
subjects affected / exposed	5 / 285 (1.75%)	2 / 282 (0.71%)	2 / 274 (0.73%)	3 / 285 (1.05%)
occurrences all number	5	2	2	3
Local swelling
Additional description: Local swelling
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Malaise
Additional description: Malaise
subjects affected / exposed	2 / 285 (0.70%)	5 / 282 (1.77%)	3 / 274 (1.09%)	2 / 285 (0.70%)
occurrences all number	2	5	3	2
Non-cardiac chest pain
Additional description: Non-cardiac chest pain
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Oedema peripheral
Additional description: Oedema peripheral
subjects affected / exposed	0 / 285 (0.00%)	13 / 282 (4.61%)	2 / 274 (0.73%)	4 / 285 (1.40%)
occurrences all number	0	16	3	4
Pain
Additional description: Pain
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	1	0	0	1
Sensation of pressure
Additional description: Sensation of pressure
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Thirst
Additional description: Thirst
subjects affected / exposed	2 / 285 (0.70%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	2	0	0	0
Immune system disorders
Hypersensitivity
Additional description: Hypersensitivity
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Seasonal allergy
Additional description: Seasonal allergy
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	1	1	0
Social circumstances
Menopause
Additional description: Menopause
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Stress at work
Additional description: Stress at work
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Reproductive system and breast disorders
Breast enlargement
Additional description: Breast enlargement
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Breast pain
Additional description: Breast pain
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Breast swelling
Additional description: Breast swelling
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Breast tenderness
Additional description: Breast tenderness
subjects affected / exposed	1 / 285 (0.35%)	1 / 282 (0.35%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	1	1	1	0
Erectile dysfunction
Additional description: Erectile dysfunction
subjects affected / exposed	2 / 285 (0.70%)	2 / 282 (0.71%)	1 / 274 (0.36%)	2 / 285 (0.70%)
occurrences all number	2	2	1	2
Menorrhagia
Additional description: Menorrhagia
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Menstrual disorder
Additional description: Menstrual disorder
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Menstruation irregular
Additional description: Menstruation irregular
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Nipple pain
Additional description: Nipple pain
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	1	0	0	1
Prostatomegaly
Additional description: Prostatomegaly
subjects affected / exposed	1 / 285 (0.35%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	1	0	0
Sexual dysfunction
Additional description: Sexual dysfunction
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
Additional description: Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Cough
Additional description: Cough
subjects affected / exposed	8 / 285 (2.81%)	6 / 282 (2.13%)	6 / 274 (2.19%)	12 / 285 (4.21%)
occurrences all number	8	6	6	12
Dyspnoea
Additional description: Dyspnoea
subjects affected / exposed	6 / 285 (2.11%)	12 / 282 (4.26%)	3 / 274 (1.09%)	7 / 285 (2.46%)
occurrences all number	6	12	4	7
Dyspnoea exertional
Additional description: Dyspnoea exertional
subjects affected / exposed	1 / 285 (0.35%)	8 / 282 (2.84%)	0 / 274 (0.00%)	4 / 285 (1.40%)
occurrences all number	1	8	0	4
Epistaxis
Additional description: Epistaxis
subjects affected / exposed	2 / 285 (0.70%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	2	0	0	1
Increased upper airway secretion
Additional description: Increased upper airway secretion
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Nasal congestion
Additional description: Nasal congestion
subjects affected / exposed	0 / 285 (0.00%)	2 / 282 (0.71%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	3	1	0
Nocturnal dyspnoea
Additional description: Nocturnal dyspnoea
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Oropharyngeal pain
Additional description: Oropharyngeal pain
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	2 / 274 (0.73%)	2 / 285 (0.70%)
occurrences all number	1	0	2	2
Pleurisy
Additional description: Pleurisy
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Productive cough
Additional description: Productive cough
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Reflux laryngitis
Additional description: Reflux laryngitis
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Respiratory tract congestion
Additional description: Respiratory tract congestion
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Respiratory tract inflammation
Additional description: Respiratory tract inflammation
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Sinus congestion
Additional description: Sinus congestion
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Throat tightness
Additional description: Throat tightness
subjects affected / exposed	0 / 285 (0.00%)	2 / 282 (0.71%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	2	0	0
Wheezing
Additional description: Wheezing
subjects affected / exposed	2 / 285 (0.70%)	5 / 282 (1.77%)	1 / 274 (0.36%)	4 / 285 (1.40%)
occurrences all number	2	5	1	4
Psychiatric disorders
Abnormal dreams
Additional description: Abnormal dreams
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	1 / 274 (0.36%)	1 / 285 (0.35%)
occurrences all number	0	1	1	1
Anxiety
Additional description: Anxiety
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Depressed mood
Additional description: Depressed mood
subjects affected / exposed	0 / 285 (0.00%)	2 / 282 (0.71%)	0 / 274 (0.00%)	2 / 285 (0.70%)
occurrences all number	0	2	0	2
Depression
Additional description: Depression
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Depression suicidal
Additional description: Depression suicidal
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Disorientation
Additional description: Disorientation
subjects affected / exposed	0 / 285 (0.00%)	3 / 282 (1.06%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	3	0	1
Hallucination
Additional description: Hallucination
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Insomnia
Additional description: Insomnia
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	1	1	0
Loss of libido
Additional description: Loss of libido
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Sleep disorder
Additional description: Sleep disorder
subjects affected / exposed	2 / 285 (0.70%)	0 / 282 (0.00%)	1 / 274 (0.36%)	2 / 285 (0.70%)
occurrences all number	2	0	1	2
Investigations
Arthroscopy
Additional description: Arthroscopy
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Biopsy prostate
Additional description: Biopsy prostate
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Blood albumin abnormal
Additional description: Blood albumin abnormal
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Blood cholesterol increased
Additional description: Blood cholesterol increased
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Blood creatine
Additional description: Blood creatine
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Blood creatinine increased
Additional description: Blood creatinine increased
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Blood glucose abnormal
Additional description: Blood glucose abnormal
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Blood glucose fluctuation
Additional description: Blood glucose fluctuation
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Blood potassium
Additional description: Blood potassium
subjects affected / exposed	2 / 285 (0.70%)	0 / 282 (0.00%)	2 / 274 (0.73%)	0 / 285 (0.00%)
occurrences all number	2	0	2	0
Blood potassium abnormal
Additional description: Blood potassium abnormal
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Blood potassium increased
Additional description: Blood potassium increased
subjects affected / exposed	4 / 285 (1.40%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	4	0	0	1
Blood pressure abnormal
Additional description: Blood pressure abnormal
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Blood sodium
Additional description: Blood sodium
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Blood sodium abnormal
Additional description: Blood sodium abnormal
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Blood sodium decreased
Additional description: Blood sodium decreased
subjects affected / exposed	3 / 285 (1.05%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	4	0	0	0
Blood test abnormal
Additional description: Blood test abnormal
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Blood triglycerides increased
Additional description: Blood triglycerides increased
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Blood urea abnormal
Additional description: Blood urea abnormal
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	1	0	1	0
Blood urea increased
Additional description: Blood urea increased
subjects affected / exposed	4 / 285 (1.40%)	1 / 282 (0.35%)	1 / 274 (0.36%)	4 / 285 (1.40%)
occurrences all number	5	1	1	7
Chlamydia test positive
Additional description: Chlamydia test positive
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Colonoscopy
Additional description: Colonoscopy
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Endoscopy
Additional description: Endoscopy
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Eosinophil count abnormal
Additional description: Eosinophil count abnormal
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Glomerular filtration rate decreased
Additional description: Glomerular filtration rate decreased
subjects affected / exposed	2 / 285 (0.70%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	2	0	0	2
Haematocrit decreased
Additional description: Haematocrit decreased
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	1	0	1
Haemoglobin decreased
Additional description: Haemoglobin decreased
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Heart rate decreased
Additional description: Heart rate decreased
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	2 / 285 (0.70%)
occurrences all number	0	1	0	2
Heart rate increased
Additional description: Heart rate increased
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Heart rate irregular
Additional description: Heart rate irregular
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Hysteroscopy
Additional description: Hysteroscopy
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Mean cell haemoglobin concentration abnormal
Additional description: Mean cell haemoglobin concentration abnormal
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Mean cell volume abnormal
Additional description: Mean cell volume abnormal
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Occult blood
Additional description: Occult blood
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Pulse abnormal
Additional description: Pulse abnormal
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Red blood cell count abnormal
Additional description: Red blood cell count abnormal
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Red blood cell morphology abnormal
Additional description: Red blood cell morphology abnormal
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Urine output decreased
Additional description: Urine output decreased
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Urine sodium increased
Additional description: Urine sodium increased
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Weight increased
Additional description: Weight increased
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Injury, poisoning and procedural complications
Arthropod bite
Additional description: Arthropod bite
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Contusion
Additional description: Contusion
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	2	0
Fall
Additional description: Fall
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	2 / 274 (0.73%)	2 / 285 (0.70%)
occurrences all number	1	0	3	2
Foot fracture
Additional description: Foot fracture
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Head injury
Additional description: Head injury
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	2
Joint dislocation
Additional description: Joint dislocation
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	2 / 274 (0.73%)	0 / 285 (0.00%)
occurrences all number	0	0	2	0
Joint sprain
Additional description: Joint sprain
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Limb injury
Additional description: Limb injury
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Meniscus lesion
Additional description: Meniscus lesion
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Muscle strain
Additional description: Muscle strain
subjects affected / exposed	2 / 285 (0.70%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	3	1	0	0
Procedural pain
Additional description: Procedural pain
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Repetitive strain injury
Additional description: Repetitive strain injury
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	2	0	0	0
Rib fracture
Additional description: Rib fracture
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Thermal burn
Additional description: Thermal burn
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Tooth injury
Additional description: Tooth injury
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Upper limb fracture
Additional description: Upper limb fracture
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Congenital, familial and genetic disorders
Thalassaemia
Additional description: Thalassaemia
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Cardiac disorders
Angina pectoris
Additional description: Angina pectoris
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	2 / 274 (0.73%)	0 / 285 (0.00%)
occurrences all number	0	0	2	0
Arrhythmia
Additional description: Arrhythmia
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Atrial fibrillation
Additional description: Atrial fibrillation
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Bradycardia
Additional description: Bradycardia
subjects affected / exposed	3 / 285 (1.05%)	2 / 282 (0.71%)	1 / 274 (0.36%)	22 / 285 (7.72%)
occurrences all number	3	2	1	22
Cardiac failure congestive
Additional description: Cardiac failure congestive
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Palpitations
Additional description: Palpitations
subjects affected / exposed	3 / 285 (1.05%)	8 / 282 (2.84%)	4 / 274 (1.46%)	3 / 285 (1.05%)
occurrences all number	3	8	5	3
Tachycardia
Additional description: Tachycardia
subjects affected / exposed	0 / 285 (0.00%)	2 / 282 (0.71%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	3	0	0
Nervous system disorders
Balance disorder
Additional description: Balance disorder
subjects affected / exposed	1 / 285 (0.35%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	1	0	0
Burning sensation
Additional description: Burning sensation
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Carpal tunnel syndrome
Additional description: Carpal tunnel syndrome
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Dizziness
Additional description: Dizziness
subjects affected / exposed	16 / 285 (5.61%)	36 / 282 (12.77%)	15 / 274 (5.47%)	17 / 285 (5.96%)
occurrences all number	16	40	15	18
Dizziness exertional
Additional description: Dizziness exertional
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Dizziness postural
Additional description: Dizziness postural
subjects affected / exposed	13 / 285 (4.56%)	5 / 282 (1.77%)	1 / 274 (0.36%)	2 / 285 (0.70%)
occurrences all number	14	5	1	2
Dysarthria
Additional description: Dysarthria
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Headache
Additional description: Headache
subjects affected / exposed	11 / 285 (3.86%)	4 / 282 (1.42%)	13 / 274 (4.74%)	10 / 285 (3.51%)
occurrences all number	15	6	14	10
Hemicephalalgia
Additional description: Hemicephalalgia
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Hypoaesthesia
Additional description: Hypoaesthesia
subjects affected / exposed	2 / 285 (0.70%)	2 / 282 (0.71%)	1 / 274 (0.36%)	5 / 285 (1.75%)
occurrences all number	2	3	1	6
Lethargy
Additional description: Lethargy
subjects affected / exposed	5 / 285 (1.75%)	4 / 282 (1.42%)	3 / 274 (1.09%)	10 / 285 (3.51%)
occurrences all number	6	4	3	10
Loss of consciousness
Additional description: Loss of consciousness
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Migraine
Additional description: Migraine
subjects affected / exposed	1 / 285 (0.35%)	1 / 282 (0.35%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	1	1	0	1
Nerve compression
Additional description: Nerve compression
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Neuropathy peripheral
Additional description: Neuropathy peripheral
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Orthostatic intolerance
Additional description: Orthostatic intolerance
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Paraesthesia
Additional description: Paraesthesia
subjects affected / exposed	4 / 285 (1.40%)	3 / 282 (1.06%)	3 / 274 (1.09%)	3 / 285 (1.05%)
occurrences all number	4	4	3	3
Parkinsonism
Additional description: Parkinsonism
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Petit mal epilepsy
Additional description: Petit mal epilepsy
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Presyncope
Additional description: Presyncope
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	1	0	1
Restless legs syndrome
Additional description: Restless legs syndrome
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Sciatica
Additional description: Sciatica
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Sensory disturbance
Additional description: Sensory disturbance
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Somnolence
Additional description: Somnolence
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	1	0	1
Syncope
Additional description: Syncope
subjects affected / exposed	1 / 285 (0.35%)	3 / 282 (1.06%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	3	0	0
Transient ischaemic attack
Additional description: Transient ischaemic attack
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Tremor
Additional description: Tremor
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	1	0	1	0
Vascular dementia
Additional description: Vascular dementia
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Blood and lymphatic system disorders
Anaemia
Additional description: Anaemia
subjects affected / exposed	2 / 285 (0.70%)	0 / 282 (0.00%)	0 / 274 (0.00%)	2 / 285 (0.70%)
occurrences all number	2	0	0	2
Ear and labyrinth disorders
Ear pain
Additional description: Ear pain
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	2 / 274 (0.73%)	0 / 285 (0.00%)
occurrences all number	0	0	2	0
Eustachian tube dysfunction
Additional description: Eustachian tube dysfunction
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Tinnitus
Additional description: Tinnitus
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Vertigo
Additional description: Vertigo
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Vertigo positional
Additional description: Vertigo positional
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	4
Eye disorders
Cataract
Additional description: Cataract
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Conjunctivitis
Additional description: Conjunctivitis
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	1	0	1
Dry eye
Additional description: Dry eye
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	1	0	1
Eye disorder
Additional description: Eye disorder
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Eye haemorrhage
Additional description: Eye haemorrhage
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Eye pain
Additional description: Eye pain
subjects affected / exposed	0 / 285 (0.00%)	2 / 282 (0.71%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	2	0	0
Lacrimation increased
Additional description: Lacrimation increased
subjects affected / exposed	2 / 285 (0.70%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	2	0	0	0
Photophobia
Additional description: Photophobia
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	1 / 285 (0.35%)
occurrences all number	0	0	1	1
Retinal disorder
Additional description: Retinal disorder
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Vision blurred
Additional description: Vision blurred
subjects affected / exposed	0 / 285 (0.00%)	3 / 282 (1.06%)	2 / 274 (0.73%)	1 / 285 (0.35%)
occurrences all number	0	3	2	1
Visual impairment
Additional description: Visual impairment
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	2	0	2	0
Vitreous floaters
Additional description: Vitreous floaters
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	2 / 274 (0.73%)	0 / 285 (0.00%)
occurrences all number	0	0	2	0
Gastrointestinal disorders
Abdominal discomfort
Additional description: Abdominal discomfort
subjects affected / exposed	1 / 285 (0.35%)	2 / 282 (0.71%)	1 / 274 (0.36%)	1 / 285 (0.35%)
occurrences all number	1	2	1	1
Abdominal distension
Additional description: Abdominal distension
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Abdominal hernia
Additional description: Abdominal hernia
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Abdominal pain
Additional description: Abdominal pain
subjects affected / exposed	2 / 285 (0.70%)	1 / 282 (0.35%)	0 / 274 (0.00%)	3 / 285 (1.05%)
occurrences all number	2	1	0	3
Abdominal pain upper
Additional description: Abdominal pain upper
subjects affected / exposed	1 / 285 (0.35%)	2 / 282 (0.71%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	1	2	0	1
Abdominal tenderness
Additional description: Abdominal tenderness
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Anal fistula
Additional description: Anal fistula
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Constipation
Additional description: Constipation
subjects affected / exposed	3 / 285 (1.05%)	2 / 282 (0.71%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	3	2	0	1
Diarrhoea
Additional description: Diarrhoea
subjects affected / exposed	2 / 285 (0.70%)	6 / 282 (2.13%)	4 / 274 (1.46%)	11 / 285 (3.86%)
occurrences all number	2	6	4	11
Dry mouth
Additional description: Dry mouth
subjects affected / exposed	2 / 285 (0.70%)	2 / 282 (0.71%)	2 / 274 (0.73%)	1 / 285 (0.35%)
occurrences all number	2	2	2	1
Dyspepsia
Additional description: Dyspepsia
subjects affected / exposed	7 / 285 (2.46%)	4 / 282 (1.42%)	2 / 274 (0.73%)	3 / 285 (1.05%)
occurrences all number	7	4	2	3
Flatulence
Additional description: Flatulence
subjects affected / exposed	2 / 285 (0.70%)	1 / 282 (0.35%)	1 / 274 (0.36%)	2 / 285 (0.70%)
occurrences all number	2	1	1	2
Frequent bowel movements
Additional description: Frequent bowel movements
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Gastrointestinal disorder
Additional description: Gastrointestinal disorder
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Gastrointestinal motility disorder
Additional description: Gastrointestinal motility disorder
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Gingival hyperplasia
Additional description: Gingival hyperplasia
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Haematochezia
Additional description: Haematochezia
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Lip swelling
Additional description: Lip swelling
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Nausea
Additional description: Nausea
subjects affected / exposed	6 / 285 (2.11%)	6 / 282 (2.13%)	2 / 274 (0.73%)	5 / 285 (1.75%)
occurrences all number	6	6	2	6
Oesophageal dilatation
Additional description: Oesophageal dilatation
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Oesophagitis
Additional description: Oesophagitis
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Oral pain
Additional description: Oral pain
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Paraesthesia oral
Additional description: Paraesthesia oral
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Rectal haemorrhage
Additional description: Rectal haemorrhage
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Toothache
Additional description: Toothache
subjects affected / exposed	2 / 285 (0.70%)	0 / 282 (0.00%)	3 / 274 (1.09%)	1 / 285 (0.35%)
occurrences all number	2	0	3	1
Vomiting
Additional description: Vomiting
subjects affected / exposed	2 / 285 (0.70%)	2 / 282 (0.71%)	1 / 274 (0.36%)	1 / 285 (0.35%)
occurrences all number	2	2	1	1
Vomiting projectile
Additional description: Vomiting projectile
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Skin and subcutaneous tissue disorders
Blister
Additional description: Blister
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	1	0	1
Cold sweat
Additional description: Cold sweat
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Dermatitis allergic
Additional description: Dermatitis allergic
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Drug eruption
Additional description: Drug eruption
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Dry skin
Additional description: Dry skin
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	1	0	1	0
Ecchymosis
Additional description: Ecchymosis
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Eczema
Additional description: Eczema
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	1	0	0	1
Erythema
Additional description: Erythema
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Hyperhidrosis
Additional description: Hyperhidrosis
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	1 / 274 (0.36%)	1 / 285 (0.35%)
occurrences all number	1	0	1	1
Intertrigo
Additional description: Intertrigo
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Pain of skin
Additional description: Pain of skin
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Papule
Additional description: Papule
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Pruritus
Additional description: Pruritus
subjects affected / exposed	4 / 285 (1.40%)	1 / 282 (0.35%)	4 / 274 (1.46%)	4 / 285 (1.40%)
occurrences all number	4	1	4	5
Pruritus generalised
Additional description: Pruritus generalised
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	1	0	1	0
Psoriasis
Additional description: Psoriasis
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Rash
Additional description: Rash
subjects affected / exposed	3 / 285 (1.05%)	4 / 282 (1.42%)	2 / 274 (0.73%)	3 / 285 (1.05%)
occurrences all number	3	5	2	3
Rash pruritic
Additional description: Rash pruritic
subjects affected / exposed	0 / 285 (0.00%)	2 / 282 (0.71%)	1 / 274 (0.36%)	1 / 285 (0.35%)
occurrences all number	0	2	1	1
Skin lesion
Additional description: Skin lesion
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	3 / 285 (1.05%)
occurrences all number	0	0	0	3
Urticaria
Additional description: Urticaria
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	1	0	1
Renal and urinary disorders
Dysuria
Additional description: Dysuria
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Haematuria
Additional description: Haematuria
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	2 / 274 (0.73%)	1 / 285 (0.35%)
occurrences all number	1	0	2	1
Incontinence
Additional description: Incontinence
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Ketonuria
Additional description: Ketonuria
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Micturition urgency
Additional description: Micturition urgency
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Nocturia
Additional description: Nocturia
subjects affected / exposed	2 / 285 (0.70%)	1 / 282 (0.35%)	0 / 274 (0.00%)	2 / 285 (0.70%)
occurrences all number	2	1	0	2
Pollakiuria
Additional description: Pollakiuria
subjects affected / exposed	4 / 285 (1.40%)	1 / 282 (0.35%)	2 / 274 (0.73%)	0 / 285 (0.00%)
occurrences all number	4	1	2	0
Polyuria
Additional description: Polyuria
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Proteinuria
Additional description: Proteinuria
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Renal colic
Additional description: Renal colic
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Renal failure chronic
Additional description: Renal failure chronic
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Renal impairment
Additional description: Renal impairment
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	1	0	0	1
Renal pain
Additional description: Renal pain
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	2	0	0	0
Urinary incontinence
Additional description: Urinary incontinence
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	1	1	0
Urinary retention
Additional description: Urinary retention
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	1	0	1	0
Urine odour abnormal
Additional description: Urine odour abnormal
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
Additional description: Arthralgia
subjects affected / exposed	6 / 285 (2.11%)	4 / 282 (1.42%)	5 / 274 (1.82%)	4 / 285 (1.40%)
occurrences all number	6	4	5	4
Arthritis
Additional description: Arthritis
subjects affected / exposed	0 / 285 (0.00%)	2 / 282 (0.71%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	2	0	1
Back pain
Additional description: Back pain
subjects affected / exposed	2 / 285 (0.70%)	3 / 282 (1.06%)	6 / 274 (2.19%)	5 / 285 (1.75%)
occurrences all number	2	3	6	5
Joint stiffness
Additional description: Joint stiffness
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	1 / 274 (0.36%)	1 / 285 (0.35%)
occurrences all number	1	0	1	1
Joint swelling
Additional description: Joint swelling
subjects affected / exposed	2 / 285 (0.70%)	12 / 282 (4.26%)	4 / 274 (1.46%)	10 / 285 (3.51%)
occurrences all number	2	12	5	10
Muscle fatigue
Additional description: Muscle fatigue
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	1	0	1
Muscle spasms
Additional description: Muscle spasms
subjects affected / exposed	22 / 285 (7.72%)	3 / 282 (1.06%)	0 / 274 (0.00%)	3 / 285 (1.05%)
occurrences all number	24	3	0	4
Muscle tightness
Additional description: Muscle tightness
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Muscle twitching
Additional description: Muscle twitching
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Muscular weakness
Additional description: Muscular weakness
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	1	1	0
Musculoskeletal discomfort
Additional description: Musculoskeletal discomfort
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Musculoskeletal pain
Additional description: Musculoskeletal pain
subjects affected / exposed	2 / 285 (0.70%)	1 / 282 (0.35%)	3 / 274 (1.09%)	3 / 285 (1.05%)
occurrences all number	2	1	3	3
Musculoskeletal stiffness
Additional description: Musculoskeletal stiffness
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	2 / 274 (0.73%)	1 / 285 (0.35%)
occurrences all number	1	0	2	1
Myalgia
Additional description: Myalgia
subjects affected / exposed	2 / 285 (0.70%)	5 / 282 (1.77%)	3 / 274 (1.09%)	2 / 285 (0.70%)
occurrences all number	2	6	3	2
Neck pain
Additional description: Neck pain
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	2 / 274 (0.73%)	0 / 285 (0.00%)
occurrences all number	0	0	2	0
Osteoarthritis
Additional description: Osteoarthritis
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Pain in extremity
Additional description: Pain in extremity
subjects affected / exposed	5 / 285 (1.75%)	3 / 282 (1.06%)	6 / 274 (2.19%)	3 / 285 (1.05%)
occurrences all number	7	3	6	3
Periarthritis
Additional description: Periarthritis
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	1	0	1	0
Plantar fasciitis
Additional description: Plantar fasciitis
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	1	0	1
Rheumatoid arthritis
Additional description: Rheumatoid arthritis
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Sensation of heaviness
Additional description: Sensation of heaviness
subjects affected / exposed	2 / 285 (0.70%)	1 / 282 (0.35%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	2	1	1	0
Tendon pain
Additional description: Tendon pain
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Infections and infestations
Abscess oral
Additional description: Abscess oral
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Body tinea
Additional description: Body tinea
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Bronchitis
Additional description: Bronchitis
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Candidiasis
Additional description: Candidiasis
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Cellulitis
Additional description: Cellulitis
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	1	0	0	1
Diverticulitis
Additional description: Diverticulitis
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	1	0	0	1
Eye infection
Additional description: Eye infection
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Fungal infection
Additional description: Fungal infection
subjects affected / exposed	1 / 285 (0.35%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	1	0	0
Furuncle
Additional description: Furuncle
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Gastroenteritis
Additional description: Gastroenteritis
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
H1N1 influenza
Additional description: H1N1 influenza
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Helicobacter infection
Additional description: Helicobacter infection
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Herpes zoster
Additional description: Herpes zoster
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Influenza
Additional description: Influenza
subjects affected / exposed	1 / 285 (0.35%)	4 / 282 (1.42%)	5 / 274 (1.82%)	2 / 285 (0.70%)
occurrences all number	1	4	5	2
Kidney infection
Additional description: Kidney infection
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Labyrinthitis
Additional description: Labyrinthitis
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Lower respiratory tract infection
Additional description: Lower respiratory tract infection
subjects affected / exposed	6 / 285 (2.11%)	2 / 282 (0.71%)	4 / 274 (1.46%)	4 / 285 (1.40%)
occurrences all number	6	2	4	4
Nasopharyngitis
Additional description: Nasopharyngitis
subjects affected / exposed	5 / 285 (1.75%)	15 / 282 (5.32%)	3 / 274 (1.09%)	9 / 285 (3.16%)
occurrences all number	5	15	3	10
Onychomycosis
Additional description: Onychomycosis
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Oral candidiasis
Additional description: Oral candidiasis
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Paronychia
Additional description: Paronychia
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	1	0	2
Pharyngitis
Additional description: Pharyngitis
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Pneumonia
Additional description: Pneumonia
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Respiratory tract infection
Additional description: Respiratory tract infection
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Rhinitis
Additional description: Rhinitis
subjects affected / exposed	2 / 285 (0.70%)	0 / 282 (0.00%)	6 / 274 (2.19%)	1 / 285 (0.35%)
occurrences all number	2	0	6	1
Sialoadenitis
Additional description: Sialoadenitis
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Sinusitis
Additional description: Sinusitis
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	2 / 274 (0.73%)	0 / 285 (0.00%)
occurrences all number	1	0	2	0
Skin infection
Additional description: Skin infection
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Tinea infection
Additional description: Tinea infection
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	1 / 285 (0.35%)
occurrences all number	0	0	1	1
Tooth abscess
Additional description: Tooth abscess
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	1	1	0
Tooth infection
Additional description: Tooth infection
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	2	0	0	0
Upper respiratory tract infection
Additional description: Upper respiratory tract infection
subjects affected / exposed	2 / 285 (0.70%)	4 / 282 (1.42%)	0 / 274 (0.00%)	2 / 285 (0.70%)
occurrences all number	2	4	0	2
Urinary tract infection
Additional description: Urinary tract infection
subjects affected / exposed	2 / 285 (0.70%)	4 / 282 (1.42%)	4 / 274 (1.46%)	4 / 285 (1.40%)
occurrences all number	2	4	4	4
Viral diarrhoea
Additional description: Viral diarrhoea
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Viral infection
Additional description: Viral infection
subjects affected / exposed	2 / 285 (0.70%)	1 / 282 (0.35%)	2 / 274 (0.73%)	0 / 285 (0.00%)
occurrences all number	2	1	2	0
Viral labyrinthitis
Additional description: Viral labyrinthitis
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Viral upper respiratory tract infection
Additional description: Viral upper respiratory tract infection
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
Additional description: Diabetes mellitus inadequate control
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Gout
Additional description: Gout
subjects affected / exposed	4 / 285 (1.40%)	4 / 282 (1.42%)	5 / 274 (1.82%)	6 / 285 (2.11%)
occurrences all number	4	4	7	7
Haemochromatosis
Additional description: Haemochromatosis
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	1 / 274 (0.36%)	0 / 285 (0.00%)
occurrences all number	0	0	1	0
Hypercalcaemia
Additional description: Hypercalcaemia
subjects affected / exposed	0 / 285 (0.00%)	0 / 282 (0.00%)	0 / 274 (0.00%)	1 / 285 (0.35%)
occurrences all number	0	0	0	1
Hyperglycaemia
Additional description: Hyperglycaemia
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0
Hyperkalaemia
Additional description: Hyperkalaemia
subjects affected / exposed	4 / 285 (1.40%)	1 / 282 (0.35%)	0 / 274 (0.00%)	2 / 285 (0.70%)
occurrences all number	6	1	0	2
Hypokalaemia
Additional description: Hypokalaemia
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Hyponatraemia
Additional description: Hyponatraemia
subjects affected / exposed	2 / 285 (0.70%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	2	0	0	0
Hypovitaminosis
Additional description: Hypovitaminosis
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Increased appetite
Additional description: Increased appetite
subjects affected / exposed	0 / 285 (0.00%)	1 / 282 (0.35%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	0	1	0	0
Salt craving
Additional description: Salt craving
subjects affected / exposed	1 / 285 (0.35%)	0 / 282 (0.00%)	0 / 274 (0.00%)	0 / 285 (0.00%)
occurrences all number	1	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

28 Aug 2009

Protocol amended to remove recruitment limiting exclusion criteria, to add pregnancy testing and other safety assessments and patient withdrawal criteria

18 Dec 2009

Protocol amended to include pharmacogentic sampling and a short patient treatment break.

26 May 2010

Protocol amended to permit a drug holiday and early randomisation. Changes to inclusion and exclusion criteria and additional visit assessments added.

10 Jan 2011

Protocol amended to remove recruitment limiting exclusion criteria and to clarify safety reporting timescales.

30 Nov 2011

Protocol amended to permit open-label (non-blinded) IMP to be used in the trial due to blinded stock issues.

23 Aug 2012

Protocol blood pressure inclusion criteria expanded to aid recruitment.

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Clinical Trial Results:
Optimal Treatment of Drug Resistant Hypertension

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: home systolic blood pressure

Primary: home systolic blood pressure

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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

Clinical trials

Clinical Trial Results: Optimal Treatment of Drug Resistant Hypertension

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: home systolic blood pressure

Primary: home systolic blood pressure

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Optimal Treatment of Drug Resistant Hypertension