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    Clinical Trial Results:
    A double blind, placebo controlled Phase 2 dose ranging study of the effects of ARA 290 on corneal nerve fiber density and neuropathic symptoms of patients with sarcoidosis

    Summary
    EudraCT number
    		 2013-003016-45
    Trial protocol
    		 NL  
    Global end of trial date
    02 Feb 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 Apr 2019
    First version publication date
    11 Apr 2019
    Other versions
    Summary report(s)
    		 Culver et al (2017) IOVS 58(6):BIO52-BIO60

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    APCP-112
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02039687
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 P13.173: LUMC protocol number
    Sponsors
    Sponsor organisation name
    Araim Pharmaceuticals, Inc.
    Sponsor organisation address
    580 White Plains Road, Suite 210, Tarrytown, United States, 10591
    Public contact
    Rita Kirk, Araim Pharmaceuticals, Inc., +1 9147627586, info@araimpharma.com
    Scientific contact
    Principal Investigator, Leiden University Medical Center, +31 0715262301, L.P.H.J.Aarts@lumc.nl
    Sponsor organisation name
    Araim Pharmaceuticals, Inc.
    Sponsor organisation address
    580 White Plains Road, Suite 210, Tarrytown, United States, 10591
    Public contact
    Rita Kirk, PhD, Araim Pharmaceuticals, Inc., +1 9147627586, rkirk@araimpharma.com
    Scientific contact
    Michael Brines, MD, PhD, Araim Pharmaceuticals, Inc., mbrines@araimpharma.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
    03 Sep 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    02 Feb 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Feb 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of different dose levels of ARA 290 administration on different outcome measures of small fiber neuropathy in subjects with sarcoidosis.
    Protection of trial subjects
    Adjustments to or Introduction of additional analgesic medication was allowed.
    Background therapy
    		 n/a
    Evidence for comparator
    		 n/a
    Actual start date of recruitment
    21 Jan 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 32
    Country: Number of subjects enrolled
    United States: 32
    Worldwide total number of subjects
    64
    EEA total number of subjects
    32
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    59
    From 65 to 84 years
    5
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 First Subject Signed the Informed Consent: 24 January 2014 Last Subject Completed Last Examination: 3 February 2015 A total of 74 subjects were enrolled and 64 subjects were randomized in The Netherlands and in The United States.

    Pre-assignment
    Screening details
    		 The main inclusion criteria were an established diagnosis of sarcoidosis with pain and reduced nerve fiber density. 74 subjects were assessed for eligibility with 10 excluded due to: nerve fiber score(n=4), lab value (n=2), Brief Pain inventory score (n=1), concomitant medication (n=1), non-compliance (n=1), and investigator decision (n=1).

    Period 1
    Period 1 title
    Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    The CRO generated the randomization code to one of the four treatment arms in a block randomization scheme, which directed all sites. At the on-site pharmacy, the study medication vials and 2 sets of boxes each containing 16 vials were labeled with the subject identification number according to the randomization code.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 1 mL placebo administered subcutaneously for 28 consecutive days
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1 mL placebo administered subcutaneously

    Arm title
    		 ARA 290 - 1 mg
    Arm description
    		 1 mg ARA 290 administered subcutaneously for 28 consecutive days
    Arm type
    		 Experimental

    Investigational medicinal product name
    ARA 290
    Investigational medicinal product code
    Other name
    Cibinetide
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1, 4, or 8 mg ARA 290 solution to be administered subcutaneously for 28 consecutive days

    Arm title
    		 ARA 290 - 4 mg
    Arm description
    		 4 mg ARA 290 administered subcutaneously for 28 consecutive days
    Arm type
    		 Experimental

    Investigational medicinal product name
    ARA 290
    Investigational medicinal product code
    Other name
    Cibinetide
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    ARA 290 solution to be administered subcutaneously

    Arm title
    		 ARA 290 - 8 mg
    Arm description
    		 8 mg ARA 290 administered subcutaneously for 28 consecutive days
    Arm type
    		 Experimental

    Investigational medicinal product name
    ARA 290
    Investigational medicinal product code
    Other name
    Cibinetide
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    1, 4, or 8 mg ARA 290 solution to be administered subcutaneously for 28 consecutive days

    Number of subjects in period 1
    		Placebo ARA 290 - 1 mg ARA 290 - 4 mg ARA 290 - 8 mg
    Started
    16
    16
    16
    16
    Completed
    16
    16
    15
    15
    Not completed
    0
    0
    1
    1
         Consent withdrawn by subject
    -
    -
    1
    -
         Adverse event, non-fatal
    -
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 1 mL placebo administered subcutaneously for 28 consecutive days

    Reporting group title
    ARA 290 - 1 mg
    Reporting group description
    		 1 mg ARA 290 administered subcutaneously for 28 consecutive days

    Reporting group title
    ARA 290 - 4 mg
    Reporting group description
    		 4 mg ARA 290 administered subcutaneously for 28 consecutive days

    Reporting group title
    ARA 290 - 8 mg
    Reporting group description
    		 8 mg ARA 290 administered subcutaneously for 28 consecutive days

    Reporting group values
    		 Placebo ARA 290 - 1 mg ARA 290 - 4 mg ARA 290 - 8 mg Total
    Number of subjects
    		 16 16 16 16 64
    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)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 15 16 13 15 59
        From 65-84 years
    		 1 0 3 1 5
        85 years and over
    		 0 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 47.8 ( 10.7 ) 51.4 ( 7.5 ) 52.0 ( 11.0 ) 52.2 ( 9.2 ) -
    Gender categorical
    Units: Subjects
        Female
    		 7 8 7 9 31
        Male
    		 9 8 9 7 33
    Change in Corneal Nerve Fiber Area
    Measurement of corneal nerve fiber area is a non-invasive procedure performed at baseline and at the end of dosing and at 12 weeks follow-up. The nerve fiber area in sarcoidosis patients is reduced compared to normal humans, a measurement of small fiber loss.
    Units: µm^2
        arithmetic mean (standard deviation)
    		 2958.2 ( 886.0 ) 2941.1 ( 1050.6 ) 2954.8 ( 629.1 ) 3191.2 ( 853.2 ) -
    Change in the 6 Minute Walk Test
    Measurement of the distance a patient can walk in 6 minutes
    Units: meters
        arithmetic mean (standard deviation)
    		 468 ( 121 ) 495 ( 109 ) 445 ( 88 ) 416 ( 110 ) -
    Change in Intra-epidermal Nerve Fiber Density (IENFD)
    Measurement of small fiber density in skin biopsies. Density is reduced in sarcoidosis patients, an indication of neuropathy.
    Units: fibers/mm
        arithmetic mean (standard deviation)
    		 4.7 ( 2.8 ) 5.2 ( 2.4 ) 6.3 ( 3.0 ) 5.1 ( 2.7 ) -
    Change in the Scores of the BPI - Pain Severity
    Brief Pain Inventory (BPI), Pain Severity - scale of 0 (no pain) to 10 (worst pain imaginable) in 4 time frames, averaged.
    Units: unit(s)
        arithmetic mean (standard deviation)
    		 5.7 ( 1.6 ) 6.1 ( 1.9 ) 6.2 ( 1.4 ) 5.8 ( 1.2 ) -
    Change in the Scores of the BPI, Pain Interference
    Brief Pain Inventory (BPI), Pain Interference - scale of 0 (does not interfere) to 10 (completely interferes) how pain interferes with 7 lifestyle parameters, averaged.
    Units: unit(s)
        arithmetic mean (standard deviation)
    		 5.6 ( 2.4 ) 6.1 ( 2.5 ) 5.8 ( 2.3 ) 6.1 ( 2.1 ) -
    Change in the Scores of the SFNSL
    Small Fiber Neuropathy Screening List (SFNSL) - scale of 0 to 84 (higher score indicates greater neuropathy), sum of 21 questions.
    Units: unit(s)
        arithmetic mean (standard deviation)
    		 38.0 ( 11.0 ) 41.4 ( 15.1 ) 42.5 ( 17.8 ) 41.2 ( 14.6 ) -
    Change in the Scores of the NPSI
    Neuropathic Pain Symptom Inventory (NPSI) - scale of 0 (least pain) to 10 (most pain) in 10 questions, summed. Total score range from 0 to 100.
    Units: unit(s)
        arithmetic mean (standard deviation)
    		 48.9 ( 20.3 ) 50.1 ( 20.0 ) 58.3 ( 20.8 ) 50.3 ( 17.1 ) -
    Change in the Scores of the FAS
    Fatigue Assessment Scale (FAS) - scale of 1 (never) to 5 (always) in 10 questions related to fatigue, summed. Total score range from 0 to 50, with 0 being the best possible score and 50 the worst
    Units: unit(s)
        arithmetic mean (standard deviation)
    		 32.6 ( 5.6 ) 33.4 ( 6.8 ) 31.8 ( 6.0 ) 32.9 ( 5.1 ) -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 1 mL placebo administered subcutaneously for 28 consecutive days

    Reporting group title
    ARA 290 - 1 mg
    Reporting group description
    		 1 mg ARA 290 administered subcutaneously for 28 consecutive days

    Reporting group title
    ARA 290 - 4 mg
    Reporting group description
    		 4 mg ARA 290 administered subcutaneously for 28 consecutive days

    Reporting group title
    ARA 290 - 8 mg
    Reporting group description
    		 8 mg ARA 290 administered subcutaneously for 28 consecutive days

    Primary: Change in Corneal Nerve Fiber Area

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    End point title
    		 Change in Corneal Nerve Fiber Area
    End point description
    Measurement of corneal nerve fiber area is a non-invasive procedure performed at baseline and at the end of dosing and at 12 weeks follow-up. The nerve fiber area in sarcoidosis patients is reduced compared to normal humans, a measurement of small fiber loss.
    End point type
    Primary
    End point timeframe
    Baseline and 28 days
    End point values
    		 Placebo ARA 290 - 1 mg ARA 290 - 4 mg ARA 290 - 8 mg
    Number of subjects analysed
    16
    16
    16
    14 [1]
    Units: µm^2
        arithmetic mean (standard deviation)
    170.0 ( 633.0 )
    -64.3 ( 759.9 )
    533.8 ( 1110.02 )
    203.8 ( 641.2 )
    Notes
    [1] - Treatment allocation could not be verified due to discrepancy in pharmacy records
    Statistical analysis title
    		 Copy of Change in corneal nerve fiber density
    Statistical analysis description
    To test the null hypothesis, p-values were provided using a paired t-test analysis within each dose group at the p = 0.05 (two-sided) significance level. The mean, standard error (SE), and 95% confidence interval (CI) for the change from baseline were reported for each treatment group.
    Comparison groups
    Placebo v ARA 290 - 8 mg
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.13
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    430.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -130.3
         upper limit
    		 992.1
    Variability estimate
    Standard deviation
    Dispersion value
    279.9
    Statistical analysis title
    		 Change in corneal nerve fiber d...
    Statistical analysis description
    To test the null hypothesis, p-values were provided using a paired t-test analysis within each dose group at the p = 0.05 (two-sided) significance level. The mean, standard error (SE), and 95% confidence interval (CI) for the change from baseline were reported for each treatment group.
    Comparison groups
    Placebo v ARA 290 - 4 mg
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.012
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    697.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 158.8
         upper limit
    		 1235.9
    Variability estimate
    Standard deviation
    Dispersion value
    268.6
    Statistical analysis title
    		 Change in corneal nerve fiber d...
    Statistical analysis description
    To test the null hypothesis, p-values were provided using a paired t-test analysis within each dose group at the p = 0.05 (two-sided) significance level. The mean, standard error (SE), and 95% confidence interval (CI) for the change from baseline were reported for each treatment group.
    Comparison groups
    Placebo v ARA 290 - 1 mg
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.686
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    109.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -429.1
         upper limit
    		 647.4
    Variability estimate
    Standard deviation
    Dispersion value
    268.5

    Secondary: Change in the 6 Minute Walk Test

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    End point title
    		 Change in the 6 Minute Walk Test
    End point description
    Measurement of the distance a patient can walk in 6 minutes
    End point type
    Secondary
    End point timeframe
    Baseline and 28 days
    End point values
    		 Placebo ARA 290 - 1 mg ARA 290 - 4 mg ARA 290 - 8 mg
    Number of subjects analysed
    16
    16
    16
    14 [2]
    Units: meter
        arithmetic mean (standard deviation)
    1.2 ( 38.56 )
    19.3 ( 79.27 )
    17.7 ( 40.29 )
    18.2 ( 47.9 )
    Notes
    [2] - Treatment allocation could not be verified due to discrepancy in pharmacy records
    No statistical analyses for this end point

    Secondary: Change in Intra-epidermal Nerve Fiber Density (IENFD)

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    End point title
    		 Change in Intra-epidermal Nerve Fiber Density (IENFD)
    End point description
    Measurement of small fiber density in skin biopsies. Density is reduced in sarcoidosis patients, an indication of neuropathy.
    End point type
    Secondary
    End point timeframe
    Baseline and 28 days
    End point values
    		 Placebo ARA 290 - 1 mg ARA 290 - 4 mg ARA 290 - 8 mg
    Number of subjects analysed
    16
    16
    16
    14 [3]
    Units: fibers/mm
        arithmetic mean (standard deviation)
    0.8 ( 1.13 )
    0.5 ( 1.58 )
    0.4 ( 2.28 )
    -0.3 ( 1.81 )
    Notes
    [3] - Treatment allocation could not be verified due to discrepancy in pharmacy records (n=2)
    No statistical analyses for this end point

    Secondary: Change in the Scores of the SFNSL

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    End point title
    		 Change in the Scores of the SFNSL
    End point description
    Small Fiber Neuropathy Screening List (SFNSL) - scale of 0 to 84 (higher score indicates greater neuropathy), sum of 21 questions.
    End point type
    Secondary
    End point timeframe
    Baseline to 28 days
    End point values
    		 Placebo ARA 290 - 1 mg ARA 290 - 4 mg ARA 290 - 8 mg
    Number of subjects analysed
    15 [4]
    16
    15 [5]
    13 [6]
    Units: unit(s)
        arithmetic mean (standard deviation)
    -7.3 ( 9.50 )
    -4.9 ( 8.87 )
    -8.7 ( 14.17 )
    -5.5 ( 7.09 )
    Notes
    [4] - Questionnaires incomplete for some subjects
    [5] - Questionnaires incomplete for some subjects
    [6] - Questionnaires incomplete for some Treatment unverifiable (n=2)
    No statistical analyses for this end point

    Secondary: Change in the Scores of the BPI, Pain Severity

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    End point title
    		 Change in the Scores of the BPI, Pain Severity
    End point description
    Change in mean score from baseline to Day 28 is recorded for each outcome. Brief Pain Inventory (BPI), Pain Severity - scale of 0 (no pain) to 10 (worst pain imaginable) in 4 time frames, averaged.
    End point type
    Secondary
    End point timeframe
    Baseline to 28 days
    End point values
    		 Placebo ARA 290 - 1 mg ARA 290 - 4 mg ARA 290 - 8 mg
    Number of subjects analysed
    16
    16
    15 [7]
    13 [8]
    Units: unit(s)
        arithmetic mean (standard deviation)
    -0.922 ( 1.4429 )
    -0.594 ( 1.6680 )
    -1.167 ( 1.6894 )
    -1.115 ( 1.7067 )
    Notes
    [7] - Questionnaires incomplete for some subjects
    [8] - Questionnaires incomplete for some Treatment unverifiable (n=2)
    No statistical analyses for this end point

    Secondary: Change in the Scores of the BPI, Pain Interference

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    End point title
    		 Change in the Scores of the BPI, Pain Interference
    End point description
    BPI, Pain Interference - scale of 0 (does not interfere) to 10 (completely interferes) how pain interferes with 7 lifestyle parameters, averaged.
    End point type
    Secondary
    End point timeframe
    Baseline to 28 days
    End point values
    		 Placebo ARA 290 - 1 mg ARA 290 - 4 mg ARA 290 - 8 mg
    Number of subjects analysed
    16
    16
    15 [9]
    13 [10]
    Units: unit(s)
        arithmetic mean (standard deviation)
    -1.732 ( 2.2174 )
    -1.187 ( 1.9453 )
    -1.657 ( 1.6482 )
    -1.308 ( 2.4403 )
    Notes
    [9] - Questionnaires incomplete for some subjects
    [10] - Questionnaires incomplete for some Treatment unverifiable (n=2)
    No statistical analyses for this end point

    Secondary: Change in the Scores of the NPSI

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    End point title
    		 Change in the Scores of the NPSI
    End point description
    Neuropathic Pain Symptom Inventory (NPSI) - scale of 0 (least pain) to 10 (most pain) in 10 questions, summed. Total score range from 0 to 100.
    End point type
    Secondary
    End point timeframe
    Baseline to 28 days
    End point values
    		 Placebo ARA 290 - 1 mg ARA 290 - 4 mg ARA 290 - 8 mg
    Number of subjects analysed
    16
    16
    14 [11]
    13 [12]
    Units: unit(s)
        arithmetic mean (standard deviation)
    -12.88 ( 13.803 )
    -12.31 ( 16.074 )
    -14.50 ( 17.887 )
    -8.38 ( 12.699 )
    Notes
    [11] - Questionnaires incomplete for some subjects
    [12] - Questionnaires incomplete for some Treatment unverifiable (n=2)
    No statistical analyses for this end point

    Secondary: Change in the Scores of the FAS Questionnaire

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    End point title
    		 Change in the Scores of the FAS Questionnaire
    End point description
    Fatigue Assessment Scale (FAS) - scale of 1 (never) to 5 (always) in 10 questions related to fatigue, summed. Total score range from 0 to 50, with 0 being the best possible score and 50 the worst.
    End point type
    Secondary
    End point timeframe
    Baseline to 28 days
    End point values
    		 Placebo ARA 290 - 1 mg ARA 290 - 4 mg ARA 290 - 8 mg
    Number of subjects analysed
    16
    16
    15 [13]
    13 [14]
    Units: unit(s)
        arithmetic mean (standard deviation)
    -2.2 ( 6.00 )
    -2.6 ( 5.52 )
    -2.1 ( 5.38 )
    -3.1 ( 5.27 )
    Notes
    [13] - Questionnaires incomplete for some subjects
    [14] - Questionnaires incomplete for some Treatment unverifiable (n=2)
    No statistical analyses for this end point

    Secondary: Frequency of Adverse Events

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    End point title
    		 Frequency of Adverse Events
    End point description
    Patients reporting at least one treatment emergent adverse event (TEAE)
    End point type
    Secondary
    End point timeframe
    Continuous reporting from baseline through 16 weeks
    End point values
    		 Placebo ARA 290 - 1 mg ARA 290 - 4 mg ARA 290 - 8 mg
    Number of subjects analysed
    16
    16
    16
    14 [15]
    Units: patients
    12
    14
    11
    12
    Notes
    [15] - Treatment allocation could not be verified due to discrepancy in pharmacy records (n=2)
    No statistical analyses for this end point

    Secondary: Frequency of Serious Adverse Events

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    End point title
    		 Frequency of Serious Adverse Events
    End point description
    Patients reporting at least one serious treatment emergent adverse event (TEAE)
    End point type
    Secondary
    End point timeframe
    Continuous reporting from baseline through 16 weeks
    End point values
    		 Placebo ARA 290 - 1 mg ARA 290 - 4 mg ARA 290 - 8 mg
    Number of subjects analysed
    16
    16
    16
    14 [16]
    Units: Patients
    0
    2
    0
    1
    Notes
    [16] - Treatment allocation could not be verified due to discrepancy in pharmacy records (n=2)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    28 day treatment with 84 day follow up
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    15.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 1 mL placebo administered subcutaneously for 28 consecutive days

    Reporting group title
    ARA 290 - 1 mg
    Reporting group description
    		 1 mg ARA 290 administered subcutaneously for 28 consecutive days

    Reporting group title
    ARA 290 - 4 mg
    Reporting group description
    		 4 mg ARA 290 administered subcutaneously for 28 consecutive days

    Reporting group title
    ARA 290 - 8 mg
    Reporting group description
    		 8 mg ARA 290 administered subcutaneously for 28 consecutive days

    Serious adverse events
    		 Placebo ARA 290 - 1 mg ARA 290 - 4 mg ARA 290 - 8 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 16 (0.00%)
    2 / 16 (12.50%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (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
    Headache
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (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
    General disorders and administration site conditions
    Chest Tightness
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (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
    Gastrointestinal disorders
    Small Bowel Enteritis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (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
    Respiratory, thoracic and mediastinal disorders
    Shortness of Breath
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (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
    Psychiatric disorders
    Suicidal Ideation
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         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
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Placebo ARA 290 - 1 mg ARA 290 - 4 mg ARA 290 - 8 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 16 (75.00%)
    14 / 16 (87.50%)
    11 / 16 (68.75%)
    12 / 14 (85.71%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypotension
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    2 / 16 (12.50%)
    3 / 16 (18.75%)
    2 / 16 (12.50%)
    0 / 14 (0.00%)
         occurrences all number
    2
    4
    2
    0
    Injection site pain
         subjects affected / exposed
    4 / 16 (25.00%)
    1 / 16 (6.25%)
    1 / 16 (6.25%)
    1 / 14 (7.14%)
         occurrences all number
    4
    1
    1
    1
    Feeling abnormal
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    0
    0
    1
    Asthenia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Disease progression
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Impaired healing
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Influenza like illness
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    1
    Injection site discomfort
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Injection site haemorrhage
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Injection site irritation
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Temperature intolerance
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Immune system disorders
    Allergy to arthropod sting
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypersensitivity
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    2
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 16 (12.50%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    2
    0
    1
    Asthma
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    0
    0
    1
    Nasal congestion
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Epitaxis
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Painful respiration
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 16 (12.50%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Abnormal dreams
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Agitation
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Burnout syndrome
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    1
    Depressed mood
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Tearfulness
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Investigations
    Oxygen saturation decreased
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Injury, poisoning and procedural complications
    Wound
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Animal bite
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Epicondylitis
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    1
    Fibula fracture
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Injection related reaction
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Meniscus injury
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Muscle strain
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    1
    Post procedural haematoma
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    1
    Procedural pain
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 16 (0.00%)
    4 / 16 (25.00%)
    3 / 16 (18.75%)
    2 / 14 (14.29%)
         occurrences all number
    0
    4
    3
    2
    Muscle contractions involuntary
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Paraesthesia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Somnolence
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    1
    Tremor
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Burning sensation
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dizziness exertional
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypoaesthesia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Mental Impairment
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    1
    Presyncope
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Retrograde Amnesia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Tension headache
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    1
    Eye disorders
    Vision blurred
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    0
    0
    1
    Accommodation disorder
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    1
    Blepharitis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Conjunctival haemorrhage
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Eye irritation
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Eyelid oedema
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 16 (12.50%)
    1 / 16 (6.25%)
    2 / 14 (14.29%)
         occurrences all number
    2
    2
    1
    2
    Nausea
         subjects affected / exposed
    0 / 16 (0.00%)
    2 / 16 (12.50%)
    2 / 16 (12.50%)
    1 / 14 (7.14%)
         occurrences all number
    0
    2
    2
    1
    Abdominal Pain
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 16 (6.25%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Abnormal faeces
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    1
    Dyspepsia
         subjects affected / exposed
    0 / 16 (0.00%)
    2 / 16 (12.50%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Constipation
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    1
    Crohn's disease
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dry mouth
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Enteritis
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Eructation
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastrointestinal pain
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Salivary gland enlargement
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Toothache
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Hyperhidrosis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Pruritis
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rash macular
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rosacea
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Sticky skin
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Haematuria
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Renal failure
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    1 / 14 (7.14%)
         occurrences all number
    2
    0
    1
    1
    Pain in extremity
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    2
    0
    0
    1
    Arthralgia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Back pain
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Flank pain
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    1
    Joint stiffness
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Joint swelling
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Neck pain
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Tendonitis
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 16 (0.00%)
    3 / 16 (18.75%)
    0 / 14 (0.00%)
         occurrences all number
    2
    0
    3
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Acute sinusitis
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Atypical pneumonia
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Bacterial vaginosis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Bronchitis
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    1
    Cellulitis
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    1
    Gastroenteritis
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Mastoiditis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Meningitis aseptic
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Oral herpes
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Orchitis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Sinusitis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Streptococcal infection
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Tooth infection
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    0
    1
    Viral infection
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Metabolism and nutrition disorders
    Folate deficiency
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 14 (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.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/28475703
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