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    Clinical Trial Results:
    Protocol 271-12-205: A Phase 2 Multi-center, Randomized, Double-blind, Vehicle-controlled, Three-arm, Parallel Group Study to Assess the Safety, Tolerability, and Efficacy of Topical OPA-15406 Ointment, in Subjects With Mild/Moderate Atopic Dermatitis

    Summary
    EudraCT number
    		 2013-003899-12
    Trial protocol
    		 PL  
    Global end of trial date
    28 Jan 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Jul 2016
    First version publication date
    15 Jul 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    271-12-205
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02068352
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Otsuka Pharmaceutical Development & Commercialization, Inc.
    Sponsor organisation address
    2440 Research Boulevard, Rockville, Maryland, United States, 20850
    Public contact
    Angela Smith, Otsuka Pharmaceutical Development &Commercialization, Inc., +1 301-956-2790, angela.smith@otsuka-us.com
    Scientific contact
    Agnes Elekes, Otsuka Pharmaceutical Development &Commercialization, Inc., +1 609-720-8453, agnes.elekes@otsuka-us.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
    22 Jun 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Jan 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Jan 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of 2 concentrations of OPA-15406 ointment (0.3% weight to weight [w/w] and 1% w/w) compared to vehicle, when administered topically twice daily (BID) in participants with mild to moderate atopic dermatitis.
    Protection of trial subjects
    This trial was conducted in compliance with International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines for conducting, recording, and reporting trials, as well as for archiving essential documents. Consistent with ethical principles for the protection of human research participants, no trial procedures were performed on trial participants until written consent had been obtained from them. The informed consent form (ICF), protocol, and amendments for this trial were submitted to and approved by the institutional review board (IRB) or independent ethics committee (IEC) for each respective trial site or country.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    20 Jun 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
    United States: 85
    Country: Number of subjects enrolled
    Australia: 24
    Country: Number of subjects enrolled
    Poland: 12
    Worldwide total number of subjects
    121
    EEA total number of subjects
    12
    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)
    7
    Adolescents (12-17 years)
    17
    Adults (18-64 years)
    96
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The trial was conducted in 121 participants at 30 trial sites in 3 countries.

    Pre-assignment
    Screening details
    		 Participants had screening evaluations between 30 and 2 days before entering the 8-week treatment phase.

    Period 1
    Period 1 title
    Overall (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    During the trial, the treatment assignment code list was available only to an independent biostatistician and the clinical supply operations group. Except in cases of emergency unblinding, participants, investigational site personnel, sponsor employees, and all other trial personnel remained blinded to the identity of the treatment assignments until every participant had completed the trial and the database had been locked.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 OPA-15406 0.3% w/w
    Arm description
    		 OPA-15406 0.3% w/w ointment was applied topically BID
    Arm type
    		 Experimental

    Investigational medicinal product name
    OPA-15406 0.3% w/w
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    OPA-15406 0.3% w/w was applied topically BID for 8 weeks

    Arm title
    		 OPA-15406 1% w/w
    Arm description
    		 OPA-15406 1% w/w ointment was applied topically BID
    Arm type
    		 Experimental

    Investigational medicinal product name
    OPA-15406 1% w/w
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    OPA-15406 1% w/w was applied topically BID for 8 weeks

    Arm title
    		 Vehicle ointment
    Arm description
    		 Vehicle ointment was applied topically BID
    Arm type
    		 Vehicle ointment

    Investigational medicinal product name
    Vehicle ointment
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Ointment
    Routes of administration
    Topical use
    Dosage and administration details
    Vehicle ointment was applied topically BID for 8 weeks

    Number of subjects in period 1
    		OPA-15406 0.3% w/w OPA-15406 1% w/w Vehicle ointment
    Started
    41
    43
    37
    Completed
    31
    35
    28
    Not completed
    10
    8
    9
         Consent withdrawn by subject
    6
    3
    1
         Protocol specified withdrawal criteria
    -
    1
    -
         Adverse event
    4
    2
    7
         Lost to follow-up
    -
    2
    -
         Protocol deviation
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    OPA-15406 0.3% w/w
    Reporting group description
    		 OPA-15406 0.3% w/w ointment was applied topically BID

    Reporting group title
    OPA-15406 1% w/w
    Reporting group description
    		 OPA-15406 1% w/w ointment was applied topically BID

    Reporting group title
    Vehicle ointment
    Reporting group description
    		 Vehicle ointment was applied topically BID

    Reporting group values
    		 OPA-15406 0.3% w/w OPA-15406 1% w/w Vehicle ointment Total
    Number of subjects
    		 41 43 37 121
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 1 2 4 7
        Adolescents (12-17 years)
    		 6 7 4 17
        Adults (18-64 years)
    		 34 33 29 96
        From 65-84 years
    		 0 1 0 1
        85 years and over
    		 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 36.4 ( 15.2 ) 34.1 ( 16.5 ) 32.2 ( 15.6 ) -
    Gender categorical
    Units: Subjects
        Female
    		 27 22 23 72
        Male
    		 14 21 14 49

    End points

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    End points reporting groups
    Reporting group title
    OPA-15406 0.3% w/w
    Reporting group description
    		 OPA-15406 0.3% w/w ointment was applied topically BID

    Reporting group title
    OPA-15406 1% w/w
    Reporting group description
    		 OPA-15406 1% w/w ointment was applied topically BID

    Reporting group title
    Vehicle ointment
    Reporting group description
    		 Vehicle ointment was applied topically BID

    Primary: Incidence of success in the Overall Investigator’s Global Assessment of Disease Severity (IGA) score at Week 4 (using non-responder imputation or last observation carried forward [LOCF] imputation)

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    End point title
    		 Incidence of success in the Overall Investigator’s Global Assessment of Disease Severity (IGA) score at Week 4 (using non-responder imputation or last observation carried forward [LOCF] imputation)
    End point description
    IGA evaluation performed by a certified rater. The IGA consists of a 6-point severity scale from clear to very severe disease (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease, and 5 = very severe disease). The IGA uses clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity assessment. The IGA assessment was performed for the overall selected treatment area(s): overall percentage body surface area to be treated and additionally for the target lesion. Success was defined as a score of 0 or 1 with at least a 2-grade reduction from Baseline. In the primary analysis, participants without IGA score at Week 4 were treated as non-responders. In the sensitivity analysis, missing IGA score at Week 4 was imputed using LOCF method first and the success was defined based on the imputed IGA score.
    End point type
    Primary
    End point timeframe
    Week 4
    End point values
    		 OPA-15406 0.3% w/w OPA-15406 1% w/w Vehicle ointment
    Number of subjects analysed
    41
    43
    37
    Units: Percentage of participants
    number (not applicable)
        Week 4 (non-responder imputation) n=41, 43, 37
    14.63
    20.93
    2.7
        Week 4 (LOCF) n=40, 43, 37
    15
    20.93
    2.7
    Statistical analysis title
    		 Statistical analysis 1 at Week 4
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomised participants who received at least one dose of study medication. Per the 2-step testing procedure pre-specified in the protocol, the comparison of the success rate for Overall IGA score in OPA-15406 1% versus vehicle at Week 4 was performed first and if significant comparison was made between OPA-15406 0.3% versus vehicle ointment.
    Comparison groups
    Vehicle ointment v OPA-15406 0.3% w/w
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.069 [1]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Mean difference (final values)
    Point estimate
    11.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.08
         upper limit
    		 23.95
    Notes
    [1] - P-value was derived using Cochran-Mantel-Haenszel (CMH) test stratified by age group (< 18 or ≥ 18) and region.
    Statistical analysis title
    		 Statistical analysis 2 at Week 4
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomised participants who received at least one dose of study medication. Per the 2-step testing procedure pre-specified in the protocol, the comparison of the success rate for Overall IGA score in OPA-15406 1% versus vehicle at Week 4 was performed first and if significant comparison was made between OPA-15406 0.3% versus vehicle ointment.
    Comparison groups
    Vehicle ointment v OPA-15406 1% w/w
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0165 [2]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Mean difference (final values)
    Point estimate
    18.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.99
         upper limit
    		 31.46
    Notes
    [2] - P-value was derived using CMH test stratified by age group (< 18 or ≥ 18) and region
    Statistical analysis title
    		 Statistical analysis 3 at Week 4 (LOCF)
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomised participants who received at least one dose of study medication. Per the 2-step testing procedure pre-specified in the protocol, the comparison of the success rate for Overall IGA score in OPA-15406 1% versus vehicle at Week 4 was performed first and if significant comparison was made between OPA-15406 0.3% versus vehicle ointment.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.0617 [4]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Mean difference (final values)
    Point estimate
    12.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.06
         upper limit
    		 24.53
    Notes
    [3] - Last observation carried forward (LOCF)
    [4] - P-value was derived using CMH test stratified by age group (< 18 or ≥ 18) and region
    Statistical analysis title
    		 Statistical analysis 4 at Week 4 (LOCF)
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomised participants who received at least one dose of study medication. Per the 2-step testing procedure pre-specified in the protocol, the comparison of the success rate for Overall IGA score in OPA-15406 1% versus vehicle at Week 4 was performed first and if significant comparison was made between OPA-154060 0.3% versus vehicle ointment.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 = 0.0165 [6]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Mean difference (final values)
    Point estimate
    18.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.99
         upper limit
    		 31.46
    Notes
    [5] - LOCF
    [6] - P-value was derived using CMH test stratified by age group (< 18 or ≥ 18) and region

    Secondary: Change from Baseline in Overall IGA Score (Using MMRM analysis)

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    End point title
    		 Change from Baseline in Overall IGA Score (Using MMRM analysis)
    End point description
    The IGA evaluation was performed by a certified rater. The IGA allows for an assessment of overall disease severity at a given time point, and it consists of a 6-point severity scale from clear to very severe disease (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease, and 5 = very severe disease). The IGA uses clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity assessment. The IGA assessment was performed for the overall selected treatment area(s): overall percentage body surface area to be treated and additionally for the target lesion.
    End point type
    Secondary
    End point timeframe
    Week 4
    End point values
    		 OPA-15406 0.3% w/w OPA-15406 1% w/w Vehicle ointment
    Number of subjects analysed
    41
    43
    37
    Units: Units on a scale
    least squares mean (standard error)
        Week 4 (n=35, 40, 29)
    -0.56 ( 0.14 )
    -0.55 ( 0.13 )
    -0.09 ( 0.15 )
    Statistical analysis title
    		 Statistical analysis 1 at Week 4
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomised participants who received at least one dose of study medication.
    Comparison groups
    Vehicle ointment v OPA-15406 0.3% w/w
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0128 [7]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.84
         upper limit
    		 -0.1
    Notes
    [7] - Derived from mixed model repeated measures (MMRM) with fixed effects of treatment, region, visit, age group (< 18 or ≥ 18), and interaction of treatment by visit as terms, Baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 2 at Week 4
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomised participants who received at least one dose of study medication.
    Comparison groups
    Vehicle ointment v OPA-15406 1% w/w
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0134 [8]
    Method
    		 MMRM
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.81
         upper limit
    		 -0.1
    Notes
    [8] - Derived from mixed model repeated measures (MMRM) with fixed effects of treatment, region, visit, age group (< 18 or ≥ 18), and interaction of treatment by visit as terms, Baseline score as a covariate

    Secondary: Change From Baseline in Overall IGA Score (Using LOCF Analysis)

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    End point title
    		 Change From Baseline in Overall IGA Score (Using LOCF Analysis)
    End point description
    The IGA allows for an assessment of overall disease severity at a given time point, and it consists of a 6-point severity scale from clear to very severe disease (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease, and 5 = very severe disease). The IGA uses clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity assessment. Missing overall IGA scores at Week 4 were imputed using LOCF method.
    End point type
    Secondary
    End point timeframe
    Week 4
    End point values
    		 OPA-15406 0.3% w/w OPA-15406 1% w/w Vehicle ointment
    Number of subjects analysed
    41
    43
    37
    Units: Units on a scale
    least squares mean (standard error)
        Week 4 (n=40, 43, 37)
    -0.54 ( 0.15 )
    -0.54 ( 0.14 )
    -0.04 ( 0.15 )
    Statistical analysis title
    		 Statistical analysis at Week 4
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomised participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 = 0.0048
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.85
         upper limit
    		 -0.16
    Notes
    [9] - Analysis of covariance (ANCOVA) model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.
    Statistical analysis title
    		 Statistical analysis at Week 4
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomised participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [10]
    P-value
    		 = 0.0045
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.84
         upper limit
    		 -0.16
    Notes
    [10] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.

    Secondary: Incidence and Severity of Adverse Events (AEs).

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    End point title
    		 Incidence and Severity of Adverse Events (AEs).
    End point description
    AEs were captured for all participants from the time the informed consent was signed until end of trial. An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A serious AE (SAE) was defined as any event which resulted in death, was life-threatening, was a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, required in-patient hospitalization or prolonged hospitalization, was a congenital anomaly/birth defect, or was another medically significant event.
    End point type
    Secondary
    End point timeframe
    From signing of informed consent through Week 8.
    End point values
    		 OPA-15406 0.3% w/w OPA-15406 1% w/w Vehicle ointment
    Number of subjects analysed
    41
    43
    37
    Units: Percentage of participants
    number (not applicable)
        Treatment emergent AEs
    58.5
    41.9
    54.1
        Application site TEAEs
    26.8
    11.6
    18.9
        Serious TEAEs
    4.9
    4.7
    0
        Severe TEAEs
    12.2
    4.7
    8.1
        Severe application site TEAEs
    4.9
    0
    5.4
    No statistical analyses for this end point

    Other pre-specified: Incidence of success in the Overall IGA score at Week 8 (using Non-responder imputation or LOCF imputation)

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    End point title
    		 Incidence of success in the Overall IGA score at Week 8 (using Non-responder imputation or LOCF imputation)
    End point description
    IGA evaluation was performed by a certified rater. The IGA consists of a 6-point severity scale from clear to very severe disease (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease, and 5 = very severe disease). The IGA uses clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity assessment. The IGA assessment was performed for the overall selected treatment area(s): overall percentage body surface area to be treated and additionally for the target lesion. Success was defined as a score of 0 or 1 with at least a 2-grade reduction from Baseline. In the primary analysis, participants without IGA score available at Week 4 were treated as non-responders. In the sensitivity analysis, the missing IGA score at Week 4 was imputed using LOCF method first and the success was defined based on the imputed IGA score.
    End point type
    Other pre-specified
    End point timeframe
    Week 8
    End point values
    		 OPA-15406 0.3% w/w OPA-15406 1% w/w Vehicle ointment
    Number of subjects analysed
    41
    43
    37
    Units: Percentage of patients
    number (not applicable)
        Week 8 (non responder imputation N=41, 43, 37)
    17.07
    16.28
    10.81
        Week 8 (LOCF N=40, 43, 37)
    20
    20.93
    10.81
    Statistical analysis title
    		 Statistical analysis 1 at Week 8
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    Vehicle ointment v OPA-15406 0.3% w/w
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4173 [11]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Mean difference (final values)
    Point estimate
    6.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.99
         upper limit
    		 21.52
    Notes
    [11] - P-value was derived using CMH test stratified by age group (< 18 or ≥ 18) and region
    Statistical analysis title
    		 Statistical analysis 2 at Week 8
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4895 [12]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Mean difference (final values)
    Point estimate
    5.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.43
         upper limit
    		 20.36
    Notes
    [12] - P-value was derived using CMH test stratified by age group (< 18 or ≥ 18) and region
    Statistical analysis title
    		 Statistical analysis 3 at Week 8 (LOCF)
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomised participants who received at least one dose of study medication.
    Comparison groups
    Vehicle ointment v OPA-15406 0.3% w/w
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [13]
    P-value
    		 = 0.2677 [14]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Mean difference (final values)
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.74
         upper limit
    		 25.12
    Notes
    [13] - LOCF
    [14] - P-value was derived using CMH test stratified by age group (< 18 or ≥ 18) and region
    Statistical analysis title
    		 Satistical analysis 4 at Week 8 (LOCF)
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [15]
    P-value
    		 = 0.2319 [16]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Mean difference (final values)
    Point estimate
    10.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.63
         upper limit
    		 25.87
    Notes
    [15] - LOCF
    [16] - P-value was derived using CMH test stratified by age group (< 18 or ≥ 18) and region

    Other pre-specified: Change From Baseline in Eczema Area and Severity Index (EASI) (Using MMRM Analysis)

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    End point title
    		 Change From Baseline in Eczema Area and Severity Index (EASI) (Using MMRM Analysis)
    End point description
    The EASI evaluation assesses the extent of disease at 4 body sites and measures 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each on a scale from 0 (no disease) to 3 (very severe). The EASI scale allows for a maximum score of 72. The EASI assessment was performed on the overall body.
    End point type
    Other pre-specified
    End point timeframe
    Weeks 1, 2, 4 ,6 and 8.
    End point values
    		 OPA-15406 0.3% w/w OPA-15406 1% w/w Vehicle ointment
    Number of subjects analysed
    41
    43
    37
    Units: Units on a scale
    least squares mean (standard error)
        Week 1 (n=38, 41, 36)
    -1.47 ( 0.64 )
    -2.39 ( 0.6 )
    -0.31 ( 0.64 )
        Week 2 (n=39, 41, 21)
    -2.24 ( 0.71 )
    -3.21 ( 0.68 )
    -0.61 ( 0.74 )
        Week 4 (n=35, 40, 29)
    -2.21 ( 0.85 )
    -3.19 ( 0.8 )
    -1.1 ( 0.9 )
        Week 6 (n=32, 35, 27)
    -2.33 ( 0.87 )
    -3.36 ( 0.83 )
    -1.99 ( 0.93 )
        Week 8 (n=31, 35, 28)
    -2.6 ( 0.9 )
    -3.47 ( 0.86 )
    -1.57 ( 0.95 )
    Statistical analysis title
    		 Statistical analysis 1 at Week 1
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [17]
    P-value
    		 = 0.1221
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.65
         upper limit
    		 0.32
    Notes
    [17] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 2 at Week 1
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [18]
    P-value
    		 = 0.0056
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.54
         upper limit
    		 -0.62
    Notes
    [18] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 1 at Week 2
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [19]
    P-value
    		 = 0.0687
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.38
         upper limit
    		 0.13
    Notes
    [19] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 2 at Week 2
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [20]
    P-value
    		 = 0.0035
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.33
         upper limit
    		 -0.87
    Notes
    [20] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 1 at Week 4
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [21]
    P-value
    		 = 0.3213
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.33
         upper limit
    		 1.11
    Notes
    [21] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 2 at Week 4
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [22]
    P-value
    		 = 0.0594
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.27
         upper limit
    		 0.08
    Notes
    [22] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 1 at Week 6
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [23]
    P-value
    		 = 0.7706
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.66
         upper limit
    		 1.98
    Notes
    [23] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 2 at Week 6
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [24]
    P-value
    		 = 0.2379
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.65
         upper limit
    		 0.92
    Notes
    [24] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 1 at Week 8
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [25]
    P-value
    		 = 0.396
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.43
         upper limit
    		 1.37
    Notes
    [25] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 2 at Week 8
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [26]
    P-value
    		 = 0.1135
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.26
         upper limit
    		 0.46
    Notes
    [26] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.

    Other pre-specified: Change From Baseline in EASI (Using LOCF Analysis)

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    End point title
    		 Change From Baseline in EASI (Using LOCF Analysis)
    End point description
    The EASI evaluation assesses the extent of disease at 4 body sites and measures 4 clinical signs: (1) erythema, (2) induration/papulation, (3) excoriation, and (4) lichenification, each on a scale from 0 (no disease) to 3 (very severe). The EASI scale allows for a maximum score of 72. The EASI assessment was performed on the overall body.
    End point type
    Other pre-specified
    End point timeframe
    Weesk 1, 2, 4, 6 and 8
    End point values
    		 OPA-15406 0.3% w/w OPA-15406 1% w/w Vehicle ointment
    Number of subjects analysed
    41
    43
    37
    Units: Units on a scale
    least squares mean (standard error)
        Week 1 (n=38, 41, 36)
    -1.35 ( 0.58 )
    -2.37 ( 0.58 )
    -0.58 ( 0.58 )
        Week 2 (n=40, 43, 37)
    -2.27 ( 0.73 )
    -3.25 ( 0.69 )
    -0.54 ( 0.73 )
        Week 4 (n=40, 43, 37)
    -2 ( 0.91 )
    -3.07 ( 0.87 )
    -0.51 ( 0.92 )
        Week 6 (n=40, 43, 37)
    -1.88 ( 0.98 )
    -3.09 ( 0.93 )
    -0.89 ( 0.99 )
        Week 8 (n=40, 43, 37)
    -2.42 ( 1.01 )
    -3.36 ( 0.96 )
    -1 ( 1.02 )
    Statistical analysis title
    		 Statistical analysis 1 at Week 1
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [27]
    P-value
    		 = 0.2676
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.14
         upper limit
    		 0.6
    Notes
    [27] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.
    Statistical analysis title
    		 Statistical analysis 2 at Week 1
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [28]
    P-value
    		 = 0.0098
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.13
         upper limit
    		 -0.44
    Notes
    [28] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.
    Statistical analysis title
    		 Statistical analysis 1 at Week 2
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [29]
    P-value
    		 = 0.0463
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.43
         upper limit
    		 -0.03
    Notes
    [29] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.
    Statistical analysis title
    		 Statistical analysis 2 at Week 2
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [30]
    P-value
    		 = 0.0017
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.39
         upper limit
    		 -1.04
    Notes
    [30] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.
    Statistical analysis title
    		 Statistical analysis 1 at Week 4
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [31]
    P-value
    		 = 0.1703
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.63
         upper limit
    		 0.65
    Notes
    [31] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.
    Statistical analysis title
    		 Statistical analysis 2 at Week 4
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [32]
    P-value
    		 = 0.0176
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.67
         upper limit
    		 -0.45
    Notes
    [32] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline
    Statistical analysis title
    		 Statistical analysis 1 at Week 6
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [33]
    P-value
    		 = 0.3996
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.29
         upper limit
    		 1.32
    Notes
    [33] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.
    Statistical analysis title
    		 Statistical analysis 1 at Week 6
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [34]
    P-value
    		 = 0.3996
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.29
         upper limit
    		 1.32
    Notes
    [34] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.
    Statistical analysis title
    		 Statistical analysis 2 at Week 6
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [35]
    P-value
    		 = 0.0573
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.46
         upper limit
    		 0.07
    Notes
    [35] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.
    Statistical analysis title
    		 Statistical analysis 1 at Week 8
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [36]
    P-value
    		 = 0.2381
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.78
         upper limit
    		 0.95
    Notes
    [36] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.
    Statistical analysis title
    		 Statistical analysis 2 at Week 8
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [37]
    P-value
    		 = 0.047
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.68
         upper limit
    		 -0.03
    Notes
    [37] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.

    Other pre-specified: Change from Baseline in Visual Analog Scale (VAS) for pruritus (Using MMRM analysis)

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    End point title
    		 Change from Baseline in Visual Analog Scale (VAS) for pruritus (Using MMRM analysis)
    End point description
    At each evaluation, the participants were asked to record their current pruritus intensity over their body overall, not just within the selected treatment areas[s] (ie, intensity over the last 24 hours) on a horizontal 100-mm line marked as “No itch” on the left end and “Worst imaginable itch” on the right end. The VAS assessment was performed on the overall impression of itch on the body and not just for the selected treatment area(s) or for the target lesion.
    End point type
    Other pre-specified
    End point timeframe
    Weeks 1, 2, 4, 6 and 8
    End point values
    		 OPA-15406 0.3% w/w OPA-15406 1% w/w Vehicle ointment
    Number of subjects analysed
    41
    43
    37
    Units: Units on a scale
    least squares mean (standard error)
        Week 1 (n=38, 41, 36)
    -9.02 ( 3.91 )
    -17.58 ( 3.7 )
    -0.25 ( 3.95 )
        Week 2 (n=39, 41, 33)
    -8.94 ( 4.27 )
    -21.14 ( 4.08 )
    -6.11 ( 4.41 )
        Week 4 (n=35, 40, 29)
    -6.27 ( 4.67 )
    -16.71 ( 4.4 )
    -4.87 ( 4.96 )
        Week 6 (n=32, 35, 27)
    -9.44 ( 5.07 )
    -18.68 ( 4.83 )
    -8.61 ( 5.4 )
        Week 8 (n=31, 35, 28)
    -10.98 ( 5.12 )
    -20.71 ( 4.85 )
    -7.3 ( 5.44 )
    Statistical analysis title
    		 Statistical analysis 1 at Week 1
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    Vehicle ointment v OPA-15406 0.3% w/w
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [38]
    P-value
    		 = 0.0639
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -8.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.07
         upper limit
    		 0.52
    Notes
    [38] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 2 at Week 1
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [39]
    P-value
    		 = 0.0003
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -17.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.47
         upper limit
    		 -8.18
    Notes
    [39] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 1 at Week 2
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [40]
    P-value
    		 = 0.597
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.45
         upper limit
    		 7.77
    Notes
    [40] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 2 at Week 2
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [41]
    P-value
    		 = 0.0053
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -15.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25.5
         upper limit
    		 -4.56
    Notes
    [41] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 1 at Week 4
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [42]
    P-value
    		 = 0.8196
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.5
         upper limit
    		 10.7
    Notes
    [42] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 2 at Week 4
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [43]
    P-value
    		 = 0.0503
    Method
    		 Mixed models analysis
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.69
         upper limit
    		 0.02
    Notes
    [43] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 1 at Week 6
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [44]
    P-value
    		 = 0.9028
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.23
         upper limit
    		 12.58
    Notes
    [44] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Stastistical analysis 2 at Week 6
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [45]
    P-value
    		 = 0.1338
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -10.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.29
         upper limit
    		 3.15
    Notes
    [45] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 1 at Week 8
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [46]
    P-value
    		 = 0.5902
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -3.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.22
         upper limit
    		 9.85
    Notes
    [46] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.
    Statistical analysis title
    		 Statistical analysis 2 at Week 8
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [47]
    P-value
    		 = 0.0482
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -13.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.73
         upper limit
    		 -0.11
    Notes
    [47] - MMRM with fixed effects of treatment, region, visit, age group, interaction of treatment by visit, baseline score as a covariate.

    Other pre-specified: Change from Baseline in VAS for pruritus (Using LOCF analysis)

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    End point title
    		 Change from Baseline in VAS for pruritus (Using LOCF analysis)
    End point description
    At each evaluation, the participants were asked to record their current pruritus intensity over their body overall, not just within the selected treatment areas[s] (ie, intensity over the last 24 hours) on a horizontal 100-mm line marked as “No itch” on the left end and “Worst imaginable itch” on the right end. The VAS assessment was performed on the overall impression of itch on the body and not just for the selected treatment area(s) or for the target lesion
    End point type
    Other pre-specified
    End point timeframe
    Weeks 1, 2, 4, 6 and 8
    End point values
    		 OPA-15406 0.3% w/w OPA-15406 1% w/w Vehicle ointment
    Number of subjects analysed
    41
    43
    37
    Units: Units on a scale
    least squares mean (standard error)
        Week 1 (n=38, 41, 26)
    -9.3 ( 4.01 )
    -18.36 ( 3.8 )
    -1.1 ( 4.07 )
        Week 2 (n=40, 43, 37)
    -9.96 ( 4.5 )
    -22.15 ( 4.24 )
    -6.26 ( 4.54 )
        Week 4 (n=40, 43, 37)
    -4.05 ( 4.92 )
    -14.59 ( 4.64 )
    -3.05 ( 4.96 )
        Week 6 (n=40, 43, 37)
    -10.69 ( 5.31 )
    -20.31 ( 5 )
    -9.29 ( 5.35 )
        Week 8 (n=40, 43, 37)
    -10.01 ( 5.51 )
    -20.33 ( 5.2 )
    -7.28 ( 5.56 )
    Statistical analysis title
    		 Statistical analysis 1 at Week 1
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [48]
    P-value
    		 = 0.089
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -8.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.66
         upper limit
    		 1.27
    Notes
    [48] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.
    Statistical analysis title
    		 Statistical analysis 2 at Week 1
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [49]
    P-value
    		 = 0.0004
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -17.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.57
         upper limit
    		 -7.94
    Notes
    [49] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.
    Statistical analysis title
    		 Statistical analysis 1 at Week 2
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [50]
    P-value
    		 = 0.4853
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -3.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.21
         upper limit
    		 6.79
    Notes
    [50] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.
    Statistical analysis title
    		 Statistical analysis 2 at Week 2
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [51]
    P-value
    		 = 0.0029
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -15.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.22
         upper limit
    		 -5.57
    Notes
    [51] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.
    Statistical analysis title
    		 Statistical analysis 1 at Week 6
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [52]
    P-value
    		 = 0.8633
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.48
         upper limit
    		 10.48
    Notes
    [52] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline
    Statistical analysis title
    		 Statistical analysis 1 at Week 6
    Statistical analysis description
    ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8227
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.78
         upper limit
    		 10.97
    Statistical analysis title
    		 Statistical analysis 2 at Week 6
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [53]
    P-value
    		 = 0.0754
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -11.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.2
         upper limit
    		 1.15
    Notes
    [53] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.
    Statistical analysis title
    		 Statistical analysis 1 at Week 8
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication
    Comparison groups
    OPA-15406 0.3% w/w v Vehicle ointment
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [54]
    P-value
    		 = 0.6746
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.58
         upper limit
    		 10.12
    Notes
    [54] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.
    Statistical analysis title
    		 Statistical analysis 2 at Week 8
    Statistical analysis description
    Analysis was performed on the Efficacy Sample which include all randomized participants who received at least one dose of study medication.
    Comparison groups
    OPA-15406 1% w/w v Vehicle ointment
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [55]
    P-value
    		 = 0.0432
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -13.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25.69
         upper limit
    		 -0.4
    Notes
    [55] - ANCOVA model with treatment, region, age group as terms, and baseline score as a covariate for change from baseline.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs were captured from the time the informed consent was signed until the end of the 8-week treatment period.
    Adverse event reporting additional description
    Treatment-related AEs were followed up until resolution or until physician assesses that resolution will not be achieved. For SAEs, physician continued to report any significant follow-up information until event resolved.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    OPA-15406 0.3% w/w
    Reporting group description
    		 OPA-15406 0.3% w/w ointment was applied topically BID

    Reporting group title
    OPA-15406 1% w/w
    Reporting group description
    		 OPA-15406 1% w/w ointment was applied topically BID

    Reporting group title
    Vehicle ointment
    Reporting group description
    		 Vehicle ointment was applied topically BID

    Serious adverse events
    		 OPA-15406 0.3% w/w OPA-15406 1% w/w Vehicle ointment
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 41 (4.88%)
    2 / 43 (4.65%)
    0 / 37 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Investigations
    Liver function test abnormal
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Multiple sclerosis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Giardiasis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 OPA-15406 0.3% w/w OPA-15406 1% w/w Vehicle ointment
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    24 / 41 (58.54%)
    16 / 43 (37.21%)
    20 / 37 (54.05%)
    Injury, poisoning and procedural complications
    Excoriation
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    2 / 37 (5.41%)
         occurrences all number
    0
    0
    2
    Thermal burn
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    0
    Tooth fracture
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 37 (0.00%)
         occurrences all number
    0
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 41 (4.88%)
    3 / 43 (6.98%)
    0 / 37 (0.00%)
         occurrences all number
    2
    3
    0
    General disorders and administration site conditions
    Application site pain
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    0
    Application site irritation
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 37 (2.70%)
         occurrences all number
    0
    0
    1
    Induration
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 37 (2.70%)
         occurrences all number
    0
    0
    1
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 37 (2.70%)
         occurrences all number
    0
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    0
    Dental caries
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    0
    Diarrhoea
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 43 (4.65%)
    0 / 37 (0.00%)
         occurrences all number
    0
    4
    0
    Toothache
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    2 / 37 (5.41%)
         occurrences all number
    0
    1
    2
    Mouth haemorrhage
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 37 (2.70%)
         occurrences all number
    0
    0
    1
    Vomiting
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 43 (4.65%)
    1 / 37 (2.70%)
         occurrences all number
    0
    2
    1
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 37 (0.00%)
         occurrences all number
    0
    1
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 37 (0.00%)
         occurrences all number
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Acanthosis nigricans
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 37 (0.00%)
         occurrences all number
    0
    1
    0
    Dermatitis atopic
         subjects affected / exposed
    11 / 41 (26.83%)
    7 / 43 (16.28%)
    8 / 37 (21.62%)
         occurrences all number
    12
    7
    8
    Erythema
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    1 / 37 (2.70%)
         occurrences all number
    1
    0
    1
    Papule
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 37 (2.70%)
         occurrences all number
    0
    0
    1
    Post inflammatory pigmentation change
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    0
    Pruritus
         subjects affected / exposed
    3 / 41 (7.32%)
    0 / 43 (0.00%)
    1 / 37 (2.70%)
         occurrences all number
    3
    0
    1
    Rash vesicular
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 37 (2.70%)
         occurrences all number
    0
    0
    1
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    0
    Proteinuria
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    2
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 37 (0.00%)
         occurrences all number
    0
    1
    0
    Tendonitis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    0
    Cellulitis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    1 / 37 (2.70%)
         occurrences all number
    1
    0
    1
    Folliculitis
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 37 (2.70%)
         occurrences all number
    0
    0
    1
    Herpes zoster
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 37 (0.00%)
         occurrences all number
    0
    1
    0
    Impetigo
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 43 (4.65%)
    0 / 37 (0.00%)
         occurrences all number
    0
    2
    0
    Klebsiella infection
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    3 / 41 (7.32%)
    1 / 43 (2.33%)
    3 / 37 (8.11%)
         occurrences all number
    5
    1
    3
    Oral candidiasis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    0
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 37 (0.00%)
         occurrences all number
    0
    1
    0
    Sinusitis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 37 (0.00%)
         occurrences all number
    0
    1
    0
    Staphylococcal infection
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 37 (0.00%)
         occurrences all number
    0
    1
    0
    Tooth infection
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 37 (0.00%)
         occurrences all number
    0
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 41 (7.32%)
    1 / 43 (2.33%)
    0 / 37 (0.00%)
         occurrences all number
    3
    1
    0
    Vulvovaginal mycotic infection
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 37 (0.00%)
         occurrences all number
    0
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Mar 2014
    The main purpose of the amendment was to incorporate the results of the phase 1b trial and to adjust the number and concentrations based on the phase 1b results. This amendment also added more information regarding use in the pediatric population, language regarding additional safety review by Data Monitoring Committee, skin sensitization monitoring, and patch testing. In addition, minor changes were made to correct typographical errors.
    01 Oct 2014
    The main purpose of the amendment was to mandate discontinuation of any enrolled participant who experienced atopic dermatitis disease worsening beyond 40% body surface area. In addition, minor changes were made to correct typographical errors.

    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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