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    Clinical Trial Results:
    A Phase III Randomized Double-Blind Placebo Controlled Trial to Evaluate the Efficacy and Safety of Nitazoxanide and Nitazoxanide plus Oseltamivir in the Treatment of Acute Uncomplicated Influenza

    Summary
    EudraCT number
    		 2013-003933-14
    Trial protocol
    		 BE  
    Global end of trial date
    16 Apr 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Jul 2021
    First version publication date
    09 Jul 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    RM08-3002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01610245
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Romark Laboratories, L.C.
    Sponsor organisation address
    3000 Bayport Dr., Tampa, United States, 33607
    Public contact
    Yelen Concepcion, Romark Laboratories L.C., +1 813282 8544, Yelen.Concepcion@romark.com
    Scientific contact
    Matthew Bardin, Romark Laboratories L.C., +1 813282 8544, matthew.bardin@romark.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    28 Feb 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    16 Apr 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Apr 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    - Evaluate the effect of nitazoxanide administered 600 mg orally b.i.d. for 5 days on time to alleviation of symptoms of acute uncomplicated influenza compared to that of a placebo. - Evaluate the effect of combination therapy with nitazoxanide 600 mg plus oseltamivir 75 mg administered orally b.i.d. for 5 days on time to alleviation of symptoms of acute uncomplicated influenza compared to that of monotherapy with nitazoxanide 600 mg b.i.d. for 5 days and monotherapy with oseltamivir 75 mg b.i.d. for 5 days
    Protection of trial subjects
    There were no specific measures that were put in place to protect trial subjects beyond those in accordance with the protocol, current International Conference in Harmonization (ICH) guidelines on Good Clinical Practice (GCP), and applicable regulatory and country-specific requirements.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Mar 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 8
    Country: Number of subjects enrolled
    Australia: 117
    Country: Number of subjects enrolled
    New Zealand: 47
    Country: Number of subjects enrolled
    Canada: 48
    Country: Number of subjects enrolled
    United States: 1721
    Worldwide total number of subjects
    1941
    EEA total number of subjects
    8
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    119
    Adults (18-64 years)
    1810
    From 65 to 84 years
    12
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study was a multicenter, randomized, factorial, double-blind, placebo controlled study. Patients were selected according to the inclusion and exclusion criteria outlined in the protocol. 13 investigators in Australia, 7 investigators in New Zealand, 1 investigator in Belgium, 14 investigators in Canada and 132 investigators in the US.

    Pre-assignment
    Screening details
    		 The population studied included adults and adolescents aged 13 to 69 years of age with presence of clinical signs and/or symptoms consistent with an acute illness compatible with influenza infection. Confirmation of influenza A or B infection by one of 4 means. Onset of illness no more than 48 hours before presentation.

    Pre-assignment period milestones
    Number of subjects started
    		 2072 [1]
    Number of subjects completed
    		 1941

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Failed screening.: 131
    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: Subject was considered enrolled if he met inclusion/exclusion criteria. The pre-assignment period was the screening period.
    Period 1
    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
    Blinding implementation details
    An independent third party prepared the master randomization list and maintained the blinding of the study. Randomization was performed in blocks of four. Blocks of blinded study medication were assigned to each investigator. Each investigator then sequentially assigned treatment numbers to patients who qualified for the study. The treatment numbers appeared on the bottles containing the blinded study medication.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Nitazoxanide 600 b.i.d.
    Arm description
    		 Two nitazoxanide 300 mg tablets and one placebo capsule b.i.d. for 5 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    nitazoxanide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Two NTZ 300 mg tablets and one placebo capsule b.i.d. for 5 days

    Investigational medicinal product name
    placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    One placebo capsule b.i.d. for 5 days.

    Arm title
    		 Oseltamivir 75 mg b.i.d.
    Arm description
    		 One oseltamivir 75 mg capsule and two placebo tablets b.i.d. for 5 days.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    oseltamivir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    One OST 75 mg capsule and two placebo tablets b.i.d. for 5 days.

    Investigational medicinal product name
    placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Two placebo tablets b.i.d. for 5 days

    Arm title
    		 Nitazoxanide 600 mg tablet and oseltamivir 75 mg capsule b.i.d
    Arm description
    		 Two nitazoxanide 300 mg tablets and one oseltamivir 75 mg capsule b.i.d. for 5 days
    Arm type
    		 Experimental

    Investigational medicinal product name
    nitazoxanide and oseltamivir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Two NTZ 300 mg tablets and one OST 75 mg capsule b.i.d. for 5 days

    Arm title
    		 Placebo
    Arm description
    		 Two placebo tablets and one placebo capsule b.i.d. for 5 days
    Arm type
    		 Placebo

    Investigational medicinal product name
    N/A
    Investigational medicinal product code
    Other name
    placebo tablets, placebo capsule
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Two placebo tablets and one placebo capsule b.i.d. for 5 days

    Number of subjects in period 1
    		Nitazoxanide 600 b.i.d. Oseltamivir 75 mg b.i.d. Nitazoxanide 600 mg tablet and oseltamivir 75 mg capsule b.i.d Placebo
    Started
    484
    481
    488
    488
    Completed
    448
    450
    449
    454
    Not completed
    36
    31
    39
    34
         Consent withdrawn by subject
    18
    10
    13
    15
         Physician decision
    -
    -
    1
    1
         Adverse event, non-fatal
    2
    2
    2
    2
         Lost to follow-up
    13
    17
    19
    11
         non-compliant with study drug
    3
    -
    3
    3
         unable to attend follow up appointments
    -
    2
    1
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Nitazoxanide 600 b.i.d.
    Reporting group description
    		 Two nitazoxanide 300 mg tablets and one placebo capsule b.i.d. for 5 days.

    Reporting group title
    Oseltamivir 75 mg b.i.d.
    Reporting group description
    		 One oseltamivir 75 mg capsule and two placebo tablets b.i.d. for 5 days.

    Reporting group title
    Nitazoxanide 600 mg tablet and oseltamivir 75 mg capsule b.i.d
    Reporting group description
    		 Two nitazoxanide 300 mg tablets and one oseltamivir 75 mg capsule b.i.d. for 5 days

    Reporting group title
    Placebo
    Reporting group description
    		 Two placebo tablets and one placebo capsule b.i.d. for 5 days

    Reporting group values
    		 Nitazoxanide 600 b.i.d. Oseltamivir 75 mg b.i.d. Nitazoxanide 600 mg tablet and oseltamivir 75 mg capsule b.i.d Placebo Total
    Number of subjects
    		 484 481 488 488 1941
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 28 23 28 40 119
        Adults (18-64 years)
    		 449 457 458 446 1810
        From 65-84 years
    		 7 1 2 2 12
        85 years and over
    		 0 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    		 35.3 (13 to 68) 35.8 (13 to 65) 34.8 (13 to 68) 35.9 (13 to 69) -
    Gender categorical
    Units: Subjects
        Female
    		 274 287 295 305 1161
        Male
    		 210 194 193 183 780
    Race
    Units: Subjects
        Asian
    		 10 5 13 4 32
        Black
    		 77 75 77 74 303
        White
    		 277 284 282 278 1121
        Other
    		 120 117 116 132 485
    Smoking History
    Units: Subjects
        Current smoker
    		 93 68 85 90 336
        Past smoker
    		 45 55 46 58 204
        Never smoked
    		 346 358 357 340 1401
    Height
    Units: cm
        arithmetic mean (full range (min-max))
    		 169.5 (144 to 201) 168.4 (145 to 201) 168.1 (140 to 193) 167.9 (130 to 202) -
    Weight
    Units: kg
        arithmetic mean (full range (min-max))
    		 79.9 (36.8 to 152.9) 79.9 (39.9 to 140.6) 80.41 (40.8 to 129.7) 79.22 (41.3 to 142.9) -
    BMI
    Units: kg/m2
        arithmetic mean (full range (min-max))
    		 27.7 (15.8 to 47.7) 28.1 (16.6 to 39.9) 28.4 (16.5 to 47.2) 28.0 (16.1 to 41.2) -

    End points

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    End points reporting groups
    Reporting group title
    Nitazoxanide 600 b.i.d.
    Reporting group description
    		 Two nitazoxanide 300 mg tablets and one placebo capsule b.i.d. for 5 days.

    Reporting group title
    Oseltamivir 75 mg b.i.d.
    Reporting group description
    		 One oseltamivir 75 mg capsule and two placebo tablets b.i.d. for 5 days.

    Reporting group title
    Nitazoxanide 600 mg tablet and oseltamivir 75 mg capsule b.i.d
    Reporting group description
    		 Two nitazoxanide 300 mg tablets and one oseltamivir 75 mg capsule b.i.d. for 5 days

    Reporting group title
    Placebo
    Reporting group description
    		 Two placebo tablets and one placebo capsule b.i.d. for 5 days

    Primary: Reduce time to alleviation of all clinical symptoms of influenza

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    End point title
    		 Reduce time to alleviation of all clinical symptoms of influenza
    End point description
    Time to alleviation of all clinical symptoms of influenza (First time at when each symptom was scored as mild or absent and remained so for 24 hours) as reported by patients.
    End point type
    Primary
    End point timeframe
    Baseline through day 28.
    End point values
    		 Nitazoxanide 600 b.i.d. Oseltamivir 75 mg b.i.d. Nitazoxanide 600 mg tablet and oseltamivir 75 mg capsule b.i.d Placebo
    Number of subjects analysed
    185
    168
    177
    180
    Units: hours
        median (inter-quartile range (Q1-Q3))
    119.1 (81 to 186)
    113.7 (64 to 168)
    106.9 (61 to 179)
    116.5 (72 to 199)
    Statistical analysis title
    		 Comparison of NTZ to placebo
    Statistical analysis description
    Time to alleviation of symptoms for the NTZ group was compared to that of the placebo group using the Peto & Peto modification of the Gehan-Wilcoxon test with acetaminophen use included as a factor.
    Comparison groups
    Nitazoxanide 600 b.i.d. v Placebo
    Number of subjects included in analysis
    365
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8622
    Method
    		 Peto-Peto modification of Gehan-Wilcoxon
    Confidence interval

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    The timeframe for reporting adverse events was baseline through Day 28.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    15.1
    Reporting groups
    Reporting group title
    Nitazoxanide 600 mg b.i.d.
    Reporting group description
    		 -

    Reporting group title
    Oseltamivir 75 mg b.i.d.
    Reporting group description
    		 -

    Reporting group title
    Nitazoxanide 600 mg + Oseltamivir 75 mg b.i.d.
    Reporting group description
    		 -

    Reporting group title
    Placebo 600 mg b.i.d
    Reporting group description
    		 -

    Serious adverse events
    		 Nitazoxanide 600 mg b.i.d. Oseltamivir 75 mg b.i.d. Nitazoxanide 600 mg + Oseltamivir 75 mg b.i.d. Placebo 600 mg b.i.d
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 484 (1.24%)
    1 / 481 (0.21%)
    3 / 488 (0.61%)
    5 / 488 (1.02%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Intentional overdose
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion of etopic pregnancy
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    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
    Adverse drug reaction
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chrohn's Disease
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatis Acute
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal perforation
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cryptosporidiosis infection
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    2 / 484 (0.41%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemochromatosis
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Nitazoxanide 600 mg b.i.d. Oseltamivir 75 mg b.i.d. Nitazoxanide 600 mg + Oseltamivir 75 mg b.i.d. Placebo 600 mg b.i.d
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    128 / 484 (26.45%)
    141 / 481 (29.31%)
    155 / 488 (31.76%)
    141 / 488 (28.89%)
    Vascular disorders
    Capillary fragility
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Haematoma
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hot flush
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    1
    0
    1
    Hypertension
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    2 / 488 (0.41%)
    1 / 488 (0.20%)
         occurrences all number
    0
    1
    2
    1
    Surgical and medical procedures
    Dental operation
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Oophorectomy
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Ophthalmic fluid drainage
         subjects affected / exposed
    2 / 484 (0.41%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    2
    0
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    1
    0
    1
    Chest discomfort
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    2 / 488 (0.41%)
         occurrences all number
    0
    0
    0
    2
    Chest pain
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Chills
         subjects affected / exposed
    2 / 484 (0.41%)
    2 / 481 (0.42%)
    2 / 488 (0.41%)
    0 / 488 (0.00%)
         occurrences all number
    2
    3
    2
    0
    Device failure
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Fatigue
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    2 / 488 (0.41%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Feeling abnormal
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hernia pain
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Irritability
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    2 / 488 (0.41%)
         occurrences all number
    0
    0
    1
    2
    Malaise
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 484 (0.41%)
    3 / 481 (0.62%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    2
    3
    0
    0
    Oedema mucosal
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pain
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Spinal pain
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Thirst
         subjects affected / exposed
    1 / 484 (0.21%)
    1 / 481 (0.21%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Vessel puncture site haematoma
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Xerosis
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    1
    1
    Multiple allergies
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Reproductive system and breast disorders
    Breast tenderness
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dysmenorrhoea
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    1
    0
    0
    1
    Epididymitis
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Erectile dysfunction
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Genital discomfort
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Menstruation delayed
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Metrorrhagia
         subjects affected / exposed
    3 / 484 (0.62%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Scrotal mass
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Semen discolouration
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Testicular mass
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vaginal discharge
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cough
         subjects affected / exposed
    2 / 484 (0.41%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    1 / 488 (0.20%)
         occurrences all number
    2
    0
    1
    1
    Dyspnoea
         subjects affected / exposed
    2 / 484 (0.41%)
    2 / 481 (0.42%)
    1 / 488 (0.20%)
    6 / 488 (1.23%)
         occurrences all number
    2
    2
    1
    6
    Epistaxis
         subjects affected / exposed
    4 / 484 (0.83%)
    5 / 481 (1.04%)
    4 / 488 (0.82%)
    6 / 488 (1.23%)
         occurrences all number
    4
    5
    5
    6
    Haemoptysis
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    3 / 488 (0.61%)
         occurrences all number
    1
    0
    0
    3
    Increased upper airway secretion
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    2 / 488 (0.41%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Nasal congestion
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    3 / 488 (0.61%)
         occurrences all number
    0
    0
    0
    3
    Nasal discomfort
         subjects affected / exposed
    1 / 484 (0.21%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    1
    1
    0
    1
    Nasal mucosal disorder
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Nasal ulcer
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pharyngeal erythema
         subjects affected / exposed
    2 / 484 (0.41%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Pharyngeal oedema
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pleuritic pain
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rhinitis seasonal
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Rhinorrhoea
         subjects affected / exposed
    1 / 484 (0.21%)
    1 / 481 (0.21%)
    1 / 488 (0.20%)
    1 / 488 (0.20%)
         occurrences all number
    1
    2
    1
    1
    Rhonchi
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Sinus congestion
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    1
    0
    0
    1
    Sneezing
         subjects affected / exposed
    1 / 484 (0.21%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Snoring
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Sputum discoloured
         subjects affected / exposed
    1 / 484 (0.21%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Throat irritation
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    1
    0
    0
    1
    Upper respiratory tract congestion
         subjects affected / exposed
    2 / 484 (0.41%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Upper-airway cough syndrome
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Wheezing
         subjects affected / exposed
    3 / 484 (0.62%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    2 / 488 (0.41%)
         occurrences all number
    3
    0
    1
    2
    Psychiatric disorders
    Abnormal dreams
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Anger
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Anxiety
         subjects affected / exposed
    0 / 484 (0.00%)
    2 / 481 (0.42%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Bipolar I disorder
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Confusional state
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    2 / 488 (0.41%)
         occurrences all number
    1
    0
    0
    3
    Delirium
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Depression
         subjects affected / exposed
    1 / 484 (0.21%)
    2 / 481 (0.42%)
    1 / 488 (0.20%)
    1 / 488 (0.20%)
         occurrences all number
    1
    2
    1
    1
    Disorientation
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    1
    1
    Hallucination
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Insomnia
         subjects affected / exposed
    8 / 484 (1.65%)
    8 / 481 (1.66%)
    4 / 488 (0.82%)
    6 / 488 (1.23%)
         occurrences all number
    8
    9
    4
    6
    Middle insomnia
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Post-traumatic stress disorder
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Restlessness
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    2 / 488 (0.41%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    2
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 484 (0.21%)
    2 / 481 (0.42%)
    5 / 488 (1.02%)
    4 / 488 (0.82%)
         occurrences all number
    1
    2
    5
    4
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 484 (0.21%)
    1 / 481 (0.21%)
    1 / 488 (0.20%)
    3 / 488 (0.61%)
         occurrences all number
    1
    1
    1
    3
    Basophil count increased
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    2 / 488 (0.41%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    2
    1
    Blood bilirubin increased
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Blood cholesterol increased
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood creatinine increased
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    3 / 488 (0.61%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Blood glucose increased
         subjects affected / exposed
    1 / 484 (0.21%)
    2 / 481 (0.42%)
    2 / 488 (0.41%)
    0 / 488 (0.00%)
         occurrences all number
    1
    2
    2
    0
    Blood potassium decreased
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Blood potassium increased
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    2 / 488 (0.41%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Blood pressure increased
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    1 / 488 (0.20%)
         occurrences all number
    1
    0
    1
    1
    Blood pressure systolic increased
         subjects affected / exposed
    1 / 484 (0.21%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Blood sodium increased
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood triglycerides increased
         subjects affected / exposed
    5 / 484 (1.03%)
    3 / 481 (0.62%)
    5 / 488 (1.02%)
    6 / 488 (1.23%)
         occurrences all number
    5
    3
    5
    6
    Blood urea decreased
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    4 / 488 (0.82%)
    2 / 488 (0.41%)
         occurrences all number
    1
    0
    4
    2
    Haemoglobin decreased
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    High density lipoprotein decreased
         subjects affected / exposed
    3 / 484 (0.62%)
    0 / 481 (0.00%)
    2 / 488 (0.41%)
    2 / 488 (0.41%)
         occurrences all number
    3
    0
    2
    2
    Lipids increased
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Liver function test abnormal
         subjects affected / exposed
    3 / 484 (0.62%)
    2 / 481 (0.42%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    3
    2
    1
    0
    Low density lipoprotein increased
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Lymphocyte count increased
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Monocyte count increased
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Neutrophil count increased
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    2 / 488 (0.41%)
    0 / 488 (0.00%)
         occurrences all number
    0
    2
    2
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Platelet count increased
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Total cholesterol/HDL ratio increased
         subjects affected / exposed
    3 / 484 (0.62%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Weight increased
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    2 / 488 (0.41%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    2 / 484 (0.41%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Facial bones fracture
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Fall
         subjects affected / exposed
    0 / 484 (0.00%)
    2 / 481 (0.42%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Hand fracture
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Heat exhaustion
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Laceration
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    2 / 488 (0.41%)
         occurrences all number
    0
    0
    0
    2
    Ligament sprain
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    2 / 488 (0.41%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Muscle strain
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Post-traumatic neck syndrome
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Procedural nausea
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Road traffic accident
         subjects affected / exposed
    1 / 484 (0.21%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Seroma
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Soft tissue injury
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Spinal column injury
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Thermal burn
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Tooth fracture
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    1
    0
    1
    Tachycardia
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Nervous system disorders
    Ageusia
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Anosmia
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    2 / 488 (0.41%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Autonomic nervous system imbalance
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Burning sensation
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Convulsion
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Dizziness
         subjects affected / exposed
    12 / 484 (2.48%)
    15 / 481 (3.12%)
    15 / 488 (3.07%)
    5 / 488 (1.02%)
         occurrences all number
    16
    16
    16
    5
    Dizziness postural
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Dysgeusia
         subjects affected / exposed
    2 / 484 (0.41%)
    3 / 481 (0.62%)
    3 / 488 (0.61%)
    1 / 488 (0.20%)
         occurrences all number
    3
    3
    3
    1
    Headache
         subjects affected / exposed
    3 / 484 (0.62%)
    3 / 481 (0.62%)
    4 / 488 (0.82%)
    4 / 488 (0.82%)
         occurrences all number
    3
    6
    5
    5
    Hypoaesthesia
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypogeusia
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Migraine
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Paraesthesia
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Sciatica
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Sinus headache
         subjects affected / exposed
    1 / 484 (0.21%)
    1 / 481 (0.21%)
    2 / 488 (0.41%)
    1 / 488 (0.20%)
         occurrences all number
    1
    1
    2
    1
    Somnolence
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    4 / 488 (0.82%)
    3 / 488 (0.61%)
         occurrences all number
    0
    2
    4
    3
    Syncope
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    2 / 488 (0.41%)
         occurrences all number
    0
    1
    0
    2
    Tension headache
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    1
    0
    1
    Tremor
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 484 (0.21%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Leukocytosis
         subjects affected / exposed
    1 / 484 (0.21%)
    4 / 481 (0.83%)
    2 / 488 (0.41%)
    0 / 488 (0.00%)
         occurrences all number
    1
    4
    2
    0
    Lymph node pain
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Lymphadenopathy
         subjects affected / exposed
    2 / 484 (0.41%)
    1 / 481 (0.21%)
    2 / 488 (0.41%)
    0 / 488 (0.00%)
         occurrences all number
    2
    1
    2
    0
    Lymphopenia
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Neutropenia
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Thrombocytopenia
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Ear and labyrinth disorders
    Cerumen impaction
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Ear canal erythema
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Ear congestion
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Ear discomfort
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Ear disorder
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Ear pain
         subjects affected / exposed
    3 / 484 (0.62%)
    6 / 481 (1.25%)
    2 / 488 (0.41%)
    2 / 488 (0.41%)
         occurrences all number
    3
    7
    2
    3
    Hypoacusis
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Middle ear effusion
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Motion sickness
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Tinnitus
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    2 / 488 (0.41%)
         occurrences all number
    0
    0
    0
    2
    Tympanic membrane disorder
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Tympanic membrane hyperaemia
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vertigo
         subjects affected / exposed
    3 / 484 (0.62%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    2 / 488 (0.41%)
         occurrences all number
    3
    1
    0
    2
    Eye disorders
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Conjunctivitis
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    2 / 488 (0.41%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    2
    1
    Eye pain
         subjects affected / exposed
    1 / 484 (0.21%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Eye pruritus
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Lacrimation increased
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Ocular hyperaemia
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Photophobia
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Vision blurred
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    2 / 488 (0.41%)
         occurrences all number
    0
    1
    0
    2
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    1 / 484 (0.21%)
    1 / 481 (0.21%)
    6 / 488 (1.23%)
    5 / 488 (1.02%)
         occurrences all number
    1
    1
    6
    5
    Abdominal distension
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    3 / 488 (0.61%)
    1 / 488 (0.20%)
         occurrences all number
    0
    1
    3
    2
    Abdominal pain
         subjects affected / exposed
    4 / 484 (0.83%)
    4 / 481 (0.83%)
    7 / 488 (1.43%)
    3 / 488 (0.61%)
         occurrences all number
    5
    5
    7
    3
    Abdominal pain lower
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    10 / 484 (2.07%)
    4 / 481 (0.83%)
    11 / 488 (2.25%)
    6 / 488 (1.23%)
         occurrences all number
    10
    4
    11
    7
    Abdominal tenderness
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Change of bowel habit
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Cheilosis
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Constipation
         subjects affected / exposed
    4 / 484 (0.83%)
    2 / 481 (0.42%)
    2 / 488 (0.41%)
    3 / 488 (0.61%)
         occurrences all number
    4
    2
    2
    3
    Diarrhoea
         subjects affected / exposed
    30 / 484 (6.20%)
    12 / 481 (2.49%)
    19 / 488 (3.89%)
    24 / 488 (4.92%)
         occurrences all number
    30
    16
    20
    24
    Dry mouth
         subjects affected / exposed
    3 / 484 (0.62%)
    0 / 481 (0.00%)
    3 / 488 (0.61%)
    1 / 488 (0.20%)
         occurrences all number
    3
    0
    3
    1
    Dyspepsia
         subjects affected / exposed
    2 / 484 (0.41%)
    2 / 481 (0.42%)
    4 / 488 (0.82%)
    0 / 488 (0.00%)
         occurrences all number
    2
    2
    4
    0
    Dysphagia
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Epigastric discomfort
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Eructation
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Flatulence
         subjects affected / exposed
    4 / 484 (0.83%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    3 / 488 (0.61%)
         occurrences all number
    4
    0
    1
    3
    Frequent bowel movements
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gastric dilatation
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Gastritis
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    1 / 488 (0.20%)
         occurrences all number
    1
    0
    1
    1
    Gingival pain
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Gingival swelling
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Irritable bowel syndrome
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Lip dry
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    2 / 488 (0.41%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Mouth ulceration
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nausea
         subjects affected / exposed
    19 / 484 (3.93%)
    21 / 481 (4.37%)
    31 / 488 (6.35%)
    26 / 488 (5.33%)
         occurrences all number
    19
    22
    33
    28
    Oral disorder
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Oral mucosal erythema
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Oral pain
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Post-tussive vomiting
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    2 / 488 (0.41%)
         occurrences all number
    0
    0
    0
    2
    Rectal spasm
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Tooth impacted
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Toothache
         subjects affected / exposed
    0 / 484 (0.00%)
    2 / 481 (0.42%)
    1 / 488 (0.20%)
    1 / 488 (0.20%)
         occurrences all number
    0
    2
    1
    1
    Vomiting
         subjects affected / exposed
    11 / 484 (2.27%)
    20 / 481 (4.16%)
    31 / 488 (6.35%)
    13 / 488 (2.66%)
         occurrences all number
    11
    21
    31
    13
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Jaundice
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Cold sweat
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    1
    0
    0
    1
    Dermatitis
         subjects affected / exposed
    1 / 484 (0.21%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    1
    1
    0
    1
    Dermatitis contact
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dry skin
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Ecchymosis
         subjects affected / exposed
    1 / 484 (0.21%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Erythema
         subjects affected / exposed
    2 / 484 (0.41%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Heat rash
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Hyperhidrosis
         subjects affected / exposed
    4 / 484 (0.83%)
    2 / 481 (0.42%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    4
    2
    1
    0
    Night sweats
         subjects affected / exposed
    3 / 484 (0.62%)
    2 / 481 (0.42%)
    1 / 488 (0.20%)
    1 / 488 (0.20%)
         occurrences all number
    3
    2
    1
    1
    Pruritus
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    2 / 488 (0.41%)
         occurrences all number
    1
    0
    1
    2
    Pruritus generalised
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rash
         subjects affected / exposed
    2 / 484 (0.41%)
    2 / 481 (0.42%)
    2 / 488 (0.41%)
    4 / 488 (0.82%)
         occurrences all number
    2
    2
    2
    4
    Rash macular
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Seborrhoea
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Urticaria
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    1 / 488 (0.20%)
         occurrences all number
    1
    0
    1
    1
    Renal and urinary disorders
    Chromaturia
         subjects affected / exposed
    25 / 484 (5.17%)
    0 / 481 (0.00%)
    27 / 488 (5.53%)
    2 / 488 (0.41%)
         occurrences all number
    26
    0
    29
    2
    Dysuria
         subjects affected / exposed
    4 / 484 (0.83%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    4
    0
    1
    0
    Glycosuria
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Haematuria
         subjects affected / exposed
    3 / 484 (0.62%)
    2 / 481 (0.42%)
    4 / 488 (0.82%)
    1 / 488 (0.20%)
         occurrences all number
    3
    2
    4
    1
    Leukocyturia
         subjects affected / exposed
    1 / 484 (0.21%)
    2 / 481 (0.42%)
    1 / 488 (0.20%)
    1 / 488 (0.20%)
         occurrences all number
    1
    2
    1
    1
    Pollakiuria
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    2 / 488 (0.41%)
         occurrences all number
    0
    0
    1
    2
    Pyuria
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Renal failure
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Renal pain
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Urinary incontinence
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 484 (0.21%)
    3 / 481 (0.62%)
    1 / 488 (0.20%)
    1 / 488 (0.20%)
         occurrences all number
    1
    3
    1
    2
    Back disorder
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Back pain
         subjects affected / exposed
    1 / 484 (0.21%)
    3 / 481 (0.62%)
    5 / 488 (1.02%)
    4 / 488 (0.82%)
         occurrences all number
    1
    3
    5
    5
    Costochondritis
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Flank pain
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Joint range of motion decreased
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Joint swelling
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Metatarsalgia
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Muscle spasms
         subjects affected / exposed
    2 / 484 (0.41%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    2 / 488 (0.41%)
         occurrences all number
    2
    0
    1
    3
    Muscle tightness
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Muscular weakness
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    3 / 484 (0.62%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    2 / 484 (0.41%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    2 / 488 (0.41%)
         occurrences all number
    2
    0
    1
    2
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    2 / 488 (0.41%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Myalgia
         subjects affected / exposed
    2 / 484 (0.41%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Neck mass
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Neck pain
         subjects affected / exposed
    1 / 484 (0.21%)
    1 / 481 (0.21%)
    1 / 488 (0.20%)
    2 / 488 (0.41%)
         occurrences all number
    1
    1
    1
    2
    Pain in extremity
         subjects affected / exposed
    2 / 484 (0.41%)
    1 / 481 (0.21%)
    1 / 488 (0.20%)
    2 / 488 (0.41%)
         occurrences all number
    2
    2
    1
    2
    Pain in jaw
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Sensation of heavyness
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Infections and infestations
    Bacterial infection
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cellulitis
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    1
    0
    0
    1
    Conjunctivitis viral
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    2 / 488 (0.41%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Gingivitis
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Herpes simplex
         subjects affected / exposed
    1 / 484 (0.21%)
    1 / 481 (0.21%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Herpes zoster
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    1
    0
    1
    Hordeolum
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Infected dermal cyst
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Infectious mononucleosis
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Laryngitis
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    2 / 488 (0.41%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    2
    1
    Nasopharyngitis
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    1
    1
    Oral candidiasis
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Oral herpes
         subjects affected / exposed
    3 / 484 (0.62%)
    4 / 481 (0.83%)
    3 / 488 (0.61%)
    1 / 488 (0.20%)
         occurrences all number
    3
    4
    3
    2
    Otitis externa
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    2 / 488 (0.41%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Paronychia
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Pharyngitis
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    1 / 488 (0.20%)
    1 / 488 (0.20%)
         occurrences all number
    0
    1
    1
    1
    Pharyngitis streptococcal
         subjects affected / exposed
    2 / 484 (0.41%)
    1 / 481 (0.21%)
    2 / 488 (0.41%)
    1 / 488 (0.20%)
         occurrences all number
    2
    1
    2
    1
    Respiratory tract infection
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rhinitis
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    1
    1
    Skin infection
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Tinea cruris
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Tinea pedis
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Tonsillitis
         subjects affected / exposed
    3 / 484 (0.62%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    3
    1
    0
    1
    Tonsillitis bacterial
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Tooth abscess
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Tooth infection
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 484 (0.21%)
    2 / 481 (0.42%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    1
    2
    0
    1
    Urinary tract infection
         subjects affected / exposed
    1 / 484 (0.21%)
    3 / 481 (0.62%)
    3 / 488 (0.61%)
    0 / 488 (0.00%)
         occurrences all number
    1
    3
    3
    0
    Vaginitis bacterial
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vulvovaginal candidiasis
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Herpes simplex ophthalmic
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    4 / 484 (0.83%)
    2 / 481 (0.42%)
    3 / 488 (0.61%)
    1 / 488 (0.20%)
         occurrences all number
    4
    2
    3
    1
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    1 / 488 (0.20%)
    0 / 488 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hyperkalaemia
         subjects affected / exposed
    0 / 484 (0.00%)
    1 / 481 (0.21%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hyperlipidaemia
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Hypoglycaemia
         subjects affected / exposed
    0 / 484 (0.00%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    1 / 488 (0.20%)
         occurrences all number
    0
    0
    0
    1
    Diabetes mellitus
         subjects affected / exposed
    1 / 484 (0.21%)
    0 / 481 (0.00%)
    0 / 488 (0.00%)
    0 / 488 (0.00%)
         occurrences all number
    1
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Methods for collecting patient-reported symptom data and measuring symptoms lacked validity. "Alleviation of symptoms" endpoint was not supported by evidence of meaningfulness to patients. Validated methods in this research area are needed.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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