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    Clinical Trial Results:
    A randomised, mono-center, placebo-controlled, double-blind, comparative study to evaluate the efficacy and safety of Dynexan® Mundgel in minors with acute painful sites of the mouth.

    Summary
    EudraCT number
    		 2011-005336-25
    Trial protocol
    		 DE  
    Global end of trial date
    04 Jul 2014

    Results information
    Results version number
    		 v2(current)
    This version publication date
    02 Feb 2016
    First version publication date
    15 May 2015
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Correction of "Routes of Administration" for IMP 2 (Placebo Gel)
    Summary report(s)
    		 Clinical Study Report Synopsis

    Trial information

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    Trial identification
    Sponsor protocol code
    DMKS-2011
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Study Code CRO: 11ct/am29dy
    Sponsors
    Sponsor organisation name
    Chemische Fabrik Kreussler & Co. GmbH
    Sponsor organisation address
    Rheingaustraße 87-93, Wiesbaden, Germany, 65203
    Public contact
    Medical-Scientific Director, Kreussler Pharma Medical Scientific Department, 49 611 9271-0, info@kreussler.com
    Scientific contact
    Medical-Scientific Director, Kreussler Pharma Medical Scientific Department, 49 611 9271-0, info@kreussler.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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    10 Jul 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    14 Jun 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Jul 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective is the comparison of pain reduction after local application of Dynexan® Mundgel or placebo on painful sites in the mouth.
    Protection of trial subjects
    The Guidelines of the World Medical Association Declaration of Helsinki 2013, the Guidelines of ICH Good Clinical Practice (GCP) (CPMP/ICH/135/95) as well as the requirements of national drug and data protection laws, and other applicable regulatory requirements were strictly followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Mar 2012
    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
    Germany: 161
    Worldwide total number of subjects
    161
    EEA total number of subjects
    161
    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)
    21
    Children (2-11 years)
    140
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The first patient was included into the trial on 21.05.2012 and the last patient completed the trial on 14.06.2014. Posters, flyers as well as newspaper advertisements were used to recruit the patients and all recruitment materials were submitted to the Independent Ethics Committee for approval prior to use.

    Pre-assignment
    Screening details
    		 To find a pool of eligible subjects, 269 subjects were pre-screened by telephone, out of which 195 presented themselves at the study centre. In case of 33 patients it was obvious even before any investigations started that these patients could not pass the inclusion/exclusion criteria. In summary 161 individual subjects were included in the study.

    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
    Age Group II was treated with verum only.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Age Group I Verum
    Arm description
    		 Minors from 4 years to 8 years
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dynexan Mundgel
    Investigational medicinal product code
    IMP 1
    Other name
    Pharmaceutical forms
    Oral gel
    Routes of administration
    Topical use
    Dosage and administration details
    Single local application of 0.2 g gel, corresponding to a pea size amount of gel

    Arm title
    		 Age Group I Placebo
    Arm description
    		 Minors from 4 years to 8 years
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo Gel
    Investigational medicinal product code
    IMP 2
    Other name
    Pharmaceutical forms
    Oral gel
    Routes of administration
    Topical use
    Dosage and administration details
    Single local application of 0.2 g gel, corresponding to a pea size amount of gel

    Arm title
    		 Age Group II
    Arm description
    		 Minors from 6 months to 3 years
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dynexan Mundgel
    Investigational medicinal product code
    IMP 1
    Other name
    Pharmaceutical forms
    Oral gel
    Routes of administration
    Topical use
    Dosage and administration details
    Single local application of 0.2 g gel, corresponding to a pea size amount of gel

    Number of subjects in period 1
    		Age Group I Verum Age Group I Placebo Age Group II
    Started
    63
    66
    32
    Completed
    63
    66
    32

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall Trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall Trial Total
    Number of subjects
    		 161 161
    Age categorical
    Minors from 4 years to 8 years
    Units: Subjects
        Age group I 4 - 8 Years
    		 129 129
        Age group II 6 months - 3 years
    		 32 32
    Gender categorical
    Units: Subjects
        Female
    		 91 91
        Male
    		 70 70

    End points

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    End points reporting groups
    Reporting group title
    Age Group I Verum
    Reporting group description
    		 Minors from 4 years to 8 years

    Reporting group title
    Age Group I Placebo
    Reporting group description
    		 Minors from 4 years to 8 years

    Reporting group title
    Age Group II
    Reporting group description
    		 Minors from 6 months to 3 years

    Primary: Pain reduction from T1 (prior to administration) to T2

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    End point title
    		 Pain reduction from T1 (prior to administration) to T2 [1]
    End point description
    The Wong-Baker FACES Pain Rating Scale is a self-report measure used to assess the intensity of children’s pain. The minors were instructed to indicate their pain by pointing to one of the faces (0 No Hurt; 1 Hurts Little Bit; 2 Hurts Little More; 3 Hurts Even More; 4 Hurts Whole Lot; 5 Hurts Worst). Pain assessment using Wong-Baker FACES Pain Rating Scale was performed in children from 4 years on. Assessment by parents was done prior to assessment by the children. If the child was not old enough and/or not able to use this scale instead of child’s assessment, the pain assessment by parents was used.
    End point type
    Primary
    End point timeframe
    Pain reduction from T1 (prior to administration) to T2 (10 ± 5 min p.a.)
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Age Group II (aged < 4 years) subjects were all treated with verum, there was no control group. In order to assess the efficacy, individual pain rating shifts (before treatment - after treatment) have been evaluated. The Wilcoxon signed rank test has been applied in order to assess statistical significance of change in an explorative manner.
    End point values
    		 Age Group I Verum Age Group I Placebo
    Number of subjects analysed
    63
    66
    Units: Wong-Baker FACES Pain Rating Scale
        median (full range (min-max))
    -2 (-4 to 0)
    -1 (-4 to 2)
    Statistical analysis title
    		 Mann Whitney U-Test
    Statistical analysis description
    MWU-Test of Treatment related difference in pain assessment
    Comparison groups
    Age Group I Verum v Age Group I Placebo
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001 [2]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [2] - Non-parametric analysis (application of Mann Whitney U (MWU)-Test) of treatment related difference in pain assessment yielded statistically significance (p-value<0.001) of the observed effect.

    Secondary: Pain reduction from T1 (prior to administration) to T3

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    End point title
    		 Pain reduction from T1 (prior to administration) to T3 [3]
    End point description
    The Wong-Baker FACES Pain Rating Scale is a self-report measure used to assess the intensity of children’s pain. The minors were instructed to indicate their pain by pointing to one of the faces (0 No Hurt; 1 Hurts Little Bit; 2 Hurts Little More; 3 Hurts Even More; 4 Hurts Whole Lot; 5 Hurts Worst). Pain assessment using Wong-Baker FACES Pain Rating Scale was performed in children from 4 years on. Assessment by parents was done prior to assessment by the children. If the child was not old enough and/or not able to use this scale instead of child’s assessment, the pain assessment by parents was used.
    End point type
    Secondary
    End point timeframe
    Pain reduction from T1 (prior to administration) to T3 (30 ± 10 min p.a.)
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Age Group II (aged < 4 years) subjects were all treated with verum, there was no control group. In order to assess the efficacy, individual pain rating shifts (before treatment - after treatment) have been evaluated. The Wilcoxon signed rank test has been applied in order to assess statistical significance of change in an explorative manner.
    End point values
    		 Age Group I Verum Age Group I Placebo
    Number of subjects analysed
    63
    66
    Units: Wong-Baker FACES Pain Rating Scale
        median (full range (min-max))
    -2 (-5 to 1)
    -1 (-4 to 1)
    Statistical analysis title
    		 Mann Whitney U-Test
    Comparison groups
    Age Group I Verum v Age Group I Placebo
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.002 [4]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [4] - The non-parametric analysis (application of Mann Whitney U (MWU)-Test) of treatment related difference in pain assessment yielded a statistically significance (p-value=0.002) of the observed effect.

    Secondary: Comparison of children’s and parent’s assessment, whenever both ratings are eligible

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    End point title
    		 Comparison of children’s and parent’s assessment, whenever both ratings are eligible [5]
    End point description
    At times T1, T2 and T3 for N=115 subjects Wong-Baker FACES Pain Rating Scale assessments of minors and parents were available for evaluation of differences. An average (median) difference of “0” item scores (difference between assessment of parent and child) was consistently observed across treatments and time points. Individual assessment of pain between parents and children show a considerable range with observed differences of up to 3 scale items. On average children rated their pain slightly lower than their parents.
    End point type
    Secondary
    End point timeframe
    T1, T2 and T3
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There was only one age group II subject with available minor’s assessment, where T1, T2 and T3 related minors’ assessments were in accordance to parents’ assessments.
    End point values
    		 Age Group I Verum Age Group I Placebo
    Number of subjects analysed
    59
    56
    Units: Wong-Baker FACES Pain Rating Scale
    median (full range (min-max))
        T1
    0 (-3 to 2)
    0 (-3 to 1)
        T2
    0 (-3 to 2)
    0 (-3 to 1)
        T3
    0 (-3 to 3)
    0 (-2 to 2)
    No statistical analyses for this end point

    Secondary: Assessment of subject’s satisfaction (parent’s assessment) as rated on a 5-point verbal rating scale

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    End point title
    		 Assessment of subject’s satisfaction (parent’s assessment) as rated on a 5-point verbal rating scale
    End point description
    Assessment of subject’s satisfaction (parent’s assessment) as rated on a 5-point verbal rating scale: 1. Very unsatisfied 2. Somewhat unsatisfied 3. Slightly satisfied 4. Satisfied 5. Very satisfied
    End point type
    Secondary
    End point timeframe
    Subject’s satisfaction was assessed by parents 1 hour after administration on a 5 point verbal rating scale.
    End point values
    		 Age Group I Verum Age Group I Placebo Age Group II
    Number of subjects analysed
    63
    66
    32
    Units: 5 point verbal rating scale
        Very unsatisfied
    1
    1
    0
        Somewhat unsatisfied
    3
    2
    0
        Slightly unsatisfied
    0
    5
    0
        Satisfied
    21
    19
    8
        Very satisfied
    38
    39
    24
    Statistical analysis title
    		 Subject Satisfaction Differences: Verum/Placebo
    Statistical analysis description
    Binary categorization of subject satisfaction: Yes/No
    Comparison groups
    Age Group I Verum v Age Group I Placebo v Age Group II
    Number of subjects included in analysis
    161
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.06 [6]
    Method
    		 Chi-squared
    Confidence interval
    Notes
    [6] - Observed differences compared to placebo arm did not reach a statistical significance at α=0.05 level (χ2-Test including age group II subjects: p-value=0.060)

    Secondary: Characterisation of safety and tolerability of the investigational product considering Adverse Events in the study population, descriptive evaluation.

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    End point title
    		 Characterisation of safety and tolerability of the investigational product considering Adverse Events in the study population, descriptive evaluation.
    End point description
    7 out of 161 subjects (4.4%) reported in total 7 AEs. In age group I 2 AEs in verum and 2 AEs in placebo arm were reported. In age group II 3 AEs in verum subjects were reported. None of the AEs were assessed as study drug related (6 “not related”, 1 “unlikely”). Five out of 7 AEs were classified as mild and 2 AEs were classified as moderate. Two subjects reported a concomitant medication during the study due to an AE. All AEs resolved completely until the end of the study. No adverse event was assessed as serious, as an unexpected adverse drug reaction or other as a clinically significant adverse event.
    End point type
    Secondary
    End point timeframe
    Study Duration
    End point values
    		 Age Group I Verum Age Group I Placebo Age Group II
    Number of subjects analysed
    63
    66
    32
    Units: Adverse events
    2
    2
    3
    No statistical analyses for this end point

    Secondary: Assessment of local tolerability by the investigator

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    End point title
    		 Assessment of local tolerability by the investigator
    End point description
    Assessment of local tolerability by the investigator (descriptive evaluation): 1. Poor 2. Moderate 3. Good 4. Very Good
    End point type
    Secondary
    End point timeframe
    The local tolerability (secondary objective) has been assessed by the investigator with a 4-point verbal rating scale 1h after administration of IMP.
    End point values
    		 Age Group I Verum Age Group I Placebo Age Group II
    Number of subjects analysed
    63
    66
    32
    Units: 4 point verbal rating scale
        Poor
    0
    0
    0
        Moderate
    0
    0
    0
        Good
    0
    2
    2
        Very good
    63
    64
    30
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    21.05.2012 - 14.06.2014
    Adverse event reporting additional description
    7 out of 161 subjects (4.4%) reported in total 7 AEs. In age group I 2 AEs in verum and 2 AEs in placebo arm were reported. In age group II 3 AEs in verum subjects were reported.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Age Group II
    Reporting group description
    		 Minors from 6 months to 3 years

    Reporting group title
    Age Group I Placebo
    Reporting group description
    		 Minors from 4 years to 8 years

    Reporting group title
    Age Group I Verum
    Reporting group description
    		 Minors from 4 years to 8 years

    Serious adverse events
    		 Age Group II Age Group I Placebo Age Group I Verum
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 66 (0.00%)
    0 / 63 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Age Group II Age Group I Placebo Age Group I Verum
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 32 (9.38%)
    2 / 66 (3.03%)
    2 / 63 (3.17%)
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 66 (0.00%)
    0 / 63 (0.00%)
         occurrences all number
    1
    0
    0
    Diarrhoea
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 66 (0.00%)
    1 / 63 (1.59%)
         occurrences all number
    0
    0
    1
    Oral pain
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 66 (1.52%)
    0 / 63 (0.00%)
         occurrences all number
    0
    1
    0
    Mouth injury
         subjects affected / exposed
    0 / 32 (0.00%)
    0 / 66 (0.00%)
    1 / 63 (1.59%)
         occurrences all number
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Bronchitis
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 66 (0.00%)
    0 / 63 (0.00%)
         occurrences all number
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Excoriation
         subjects affected / exposed
    0 / 32 (0.00%)
    1 / 66 (1.52%)
    0 / 63 (0.00%)
         occurrences all number
    0
    1
    0
    Infections and infestations
    Hand-foot-and-mouth disease
         subjects affected / exposed
    1 / 32 (3.13%)
    0 / 66 (0.00%)
    0 / 63 (0.00%)
         occurrences all number
    1
    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
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    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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