Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Randomised, double-blind, placebo-controlled trial evaluating the effects of naltrexone hydrochloride nasal spray on alcohol consumption in Alcohol Use Disorder

    Summary
    EudraCT number
    		 2019-002859-42
    Trial protocol
    		 GB   HU  
    Global end of trial date
    14 Feb 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Mar 2024
    First version publication date
    16 Mar 2024
    Other versions
    Summary report(s)
    		 Clinical Study Report Synopsis

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    OPNT002-AUD-001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Opiant Pharmaceuticals
    Sponsor organisation address
    233 Wilshire Blvd., Suite 280, Santa Monica, United States, CA 90401
    Public contact
    Global Director Clinical Development, Indivior Inc., +1 804-594-4488, trialdisclosure@indivior.com
    Scientific contact
    Global Director Clinical Development, Indivior Inc., +1 804-594-4488, trialdisclosure@indivior.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
    01 Sep 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    01 Feb 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Feb 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess whether treatment with naltrexone hydrochloride nasal spray reduces drinking in patients with alcohol use disorder
    Protection of trial subjects
    Taking blood samples may cause bruising and discomfort and a risk of infection or blood clots at the site of the blood draw. The blood samples were assessed for a haematology and biochemistry panel to monitor changes in patients’ health. Blood samples were taken by trained site personnel. Patients were informed of all of the risks in the participant information sheet and were asked to notify their study doctor or study staff should they experience any side effects during the study. Patients were monitored throughout the study in order to minimise risks.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Jan 2022
    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
    Poland: 125
    Country: Number of subjects enrolled
    United Kingdom: 36
    Country: Number of subjects enrolled
    Bulgaria: 108
    Country: Number of subjects enrolled
    Hungary: 37
    Worldwide total number of subjects
    306
    EEA total number of subjects
    270
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    285
    From 65 to 84 years
    21
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Subjects were recruited from the full range of treatment services available to these subjects, directly or through advertisements. Subjects completed a telephone or in person, Screening assessment to ascertain eligibility, type and stage of illness, current medication, and treatment.

    Pre-assignment
    Screening details
    		 -

    Pre-assignment period milestones
    Number of subjects started
    		 365 [1]
    Number of subjects completed
    		 306

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Screen failure: 59
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The number of patients that started the pre-assignment period are the total patients screened. The worldwide number is the number of patients randomised. Some patients screen failed. This accounts for the discrepancy.
    Period 1
    Period 1 title
    Period 1 - week 1-8
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo nasal spray
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nasal spray
    Routes of administration
    Intranasal use
    Dosage and administration details
    Placebo (one spray of 0.1 ml of the placebo formulation), one spray in one nostril once daily

    Arm title
    		 Naltrexone 12
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Naltrexone hydrochloride nasal spray 12mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nasal spray
    Routes of administration
    Intranasal use
    Dosage and administration details
    12 mg/ml (1.2 mg: one spray of 0.1 ml of the 12 mg/ml formulation), one spray in one nostril once daily

    Arm title
    		 Naltrexone 30
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Naltrexone hydrochloride nasal spray 30mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nasal spray
    Routes of administration
    Intranasal use
    Dosage and administration details
    30 mg/ml (3 mg: one spray of 0.1 ml of the 30 mg/ml formulation), one spray in one nostril once daily

    Number of subjects in period 1
    		Placebo Naltrexone 12 Naltrexone 30
    Started
    206
    47
    53
    Completed
    187
    41
    46
    Not completed
    19
    6
    7
         Adverse event, serious fatal
    -
    1
    -
         Physician decision
    2
    -
    -
         Adverse event, non-fatal
    2
    -
    1
         Technical problems
    -
    -
    1
         Lost to follow-up
    2
    1
    1
         Subject/guardian decision
    6
    3
    2
         Protocol deviation
    7
    1
    2
    Period 2
    Period 2 title
    Period 2 - week 9-16
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo Non-responder Placebo
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo nasal spray
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nasal spray
    Routes of administration
    Intranasal use
    Dosage and administration details
    Placebo (one spray of 0.1 ml of the placebo formulation), one spray in one nostril once daily

    Arm title
    		 Placebo Non-responder Naltrexone 12
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Naltrexone hydrochloride nasal spray 12mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nasal spray
    Routes of administration
    Intranasal use
    Dosage and administration details
    12 mg/ml (1.2 mg: one spray of 0.1 ml of the 12 mg/ml formulation), one spray in one nostril once daily

    Arm title
    		 Placebo Non-responder Naltrexone 30
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Naltrexone hydrochloride nasal spray 30mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nasal spray
    Routes of administration
    Intranasal use
    Dosage and administration details
    30 mg/ml (3 mg: one spray of 0.1 ml of the 30 mg/ml formulation), one spray in one nostril once daily

    Arm title
    		 Naltrexone 12
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Naltrexone hydrochloride nasal spray 12mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nasal spray
    Routes of administration
    Intranasal use
    Dosage and administration details
    12 mg/ml (1.2 mg: one spray of 0.1 ml of the 12 mg/ml formulation), one spray in one nostril once daily

    Arm title
    		 Naltrexone 30
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Naltrexone hydrochloride nasal spray 30mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nasal spray
    Routes of administration
    Intranasal use
    Dosage and administration details
    30 mg/ml (3 mg: one spray of 0.1 ml of the 30 mg/ml formulation), one spray in one nostril once daily

    Arm title
    		 Placebo Responder Placebo
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo nasal spray
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nasal spray
    Routes of administration
    Intranasal use
    Dosage and administration details
    Placebo (one spray of 0.1 ml of the placebo formulation), one spray in one nostril once daily

    Number of subjects in period 2
    		Placebo Non-responder Placebo Placebo Non-responder Naltrexone 12 Placebo Non-responder Naltrexone 30 Naltrexone 12 Naltrexone 30 Placebo Responder Placebo
    Started
    23
    34
    30
    41
    46
    100
    Completed
    20
    28
    28
    37
    42
    92
    Not completed
    3
    6
    2
    4
    4
    8
         Physician decision
    -
    2
    -
    -
    -
    -
         Study terminated by Sponsor
    -
    1
    -
    -
    -
    -
         Technical problems
    1
    -
    -
    -
    -
    -
         Adverse event, non-fatal
    -
    -
    1
    1
    -
    2
         Lost to follow-up
    -
    2
    -
    1
    -
    2
         Subject/guardian decision
    2
    -
    1
    1
    3
    4
         Protocol deviation
    -
    1
    -
    1
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    Naltrexone 12
    Reporting group description
    		 -

    Reporting group title
    Naltrexone 30
    Reporting group description
    		 -

    Reporting group values
    		 Placebo Naltrexone 12 Naltrexone 30 Total
    Number of subjects
    		 206 47 53 306
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 191 45 49 285
        From 65-84 years
    		 15 2 4 21
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 47.4 ± 11.4 46.4 ± 10.62 45.7 ± 11.05 -
    Gender categorical
    Units: Subjects
        Female
    		 55 7 11 73
        Male
    		 151 40 42 233
    Childbearing status
    Units: Subjects
        Able to bear children
    		 30 2 6 38
        Oophorectomy
    		 0 1 0 1
        Post Menopausal
    		 22 4 5 31
        Sterile (of childbearing age)
    		 3 0 0 3
        Premenarche
    		 0 0 0 0
        N/A - Male
    		 151 40 42 233
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0
        Asian
    		 1 0 0 1
        Black or African American
    		 0 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        White
    		 205 47 53 305
        Other
    		 0 0 0 0
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 0 0 0 0
        Not Hispanic or Latino
    		 206 47 53 306
        Unknown
    		 0 0 0 0
    BMI
    Units: kg/m2
        arithmetic mean (standard deviation)
    		 26.23 ± 4.162 27.13 ± 4.146 27.48 ± 4.706 -
    Subject analysis sets

    Subject analysis set title
    Safety Analysis Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The safety analysis set consists of all randomised subjects who have at least one dose of IMP. Safety Analysis Sets included all subjects treated in each stage according to their actual treatment group.

    Subject analysis set title
    ITT I Analysis Set
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The ITT I Analysis Set consists of all subjects randomised in Stage I.

    Subject analysis set title
    ITT II Analysis Set
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    ITT II Analysis Set is a subset of ITT I and consists of only the re randomised subjects, Stage I placebo nonresponders

    Subject analysis sets values
    		 Safety Analysis Set ITT I Analysis Set ITT II Analysis Set
    Number of subjects
    306
    306
    87
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    285
    285
        From 65-84 years
    21
    21
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    47 ± 11.21
    47 ± 11.21
    46.4 ± 10.67
    Gender categorical
    Units: Subjects
        Female
    73
    73
    18
        Male
    233
    233
    69
    Childbearing status
    Units: Subjects
        Able to bear children
    38
    38
    9
        Oophorectomy
    1
    1
    0
        Post Menopausal
    31
    31
    8
        Sterile (of childbearing age)
    3
    3
    1
        Premenarche
    0
    0
    0
        N/A - Male
    233
    233
    69
    Race
    Units: Subjects
        American Indian or Alaska Native
    0
    0
    0
        Asian
    1
    1
    0
        Black or African American
    0
    0
    0
        Native Hawaiian or Other Pacific Islander
    0
    0
    0
        White
    305
    305
    87
        Other
    0
    0
    0
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    0
    0
    0
        Not Hispanic or Latino
    306
    306
    87
        Unknown
    0
    0
    0
    BMI
    Units: kg/m2
        arithmetic mean (standard deviation)
    26.58 ± 4.276
    26.58 ± 4.276
    26.34 ± 4.09

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    Naltrexone 12
    Reporting group description
    		 -

    Reporting group title
    Naltrexone 30
    Reporting group description
    		 -
    Reporting group title
    Placebo Non-responder Placebo
    Reporting group description
    		 -

    Reporting group title
    Placebo Non-responder Naltrexone 12
    Reporting group description
    		 -

    Reporting group title
    Placebo Non-responder Naltrexone 30
    Reporting group description
    		 -

    Reporting group title
    Naltrexone 12
    Reporting group description
    		 -

    Reporting group title
    Naltrexone 30
    Reporting group description
    		 -

    Reporting group title
    Placebo Responder Placebo
    Reporting group description
    		 -

    Subject analysis set title
    Safety Analysis Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The safety analysis set consists of all randomised subjects who have at least one dose of IMP. Safety Analysis Sets included all subjects treated in each stage according to their actual treatment group.

    Subject analysis set title
    ITT I Analysis Set
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The ITT I Analysis Set consists of all subjects randomised in Stage I.

    Subject analysis set title
    ITT II Analysis Set
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    ITT II Analysis Set is a subset of ITT I and consists of only the re randomised subjects, Stage I placebo nonresponders

    Primary: 2-level reduction in WHO Drinking Risk Level

    		 Close Top of page
    End point title
    		 2-level reduction in WHO Drinking Risk Level
    End point description
    The proportion of subjects who show at least a 2-level reduction in WHO Drinking Risk Level from Baseline to end of treatment (EOT) (as evaluated in the 28 days prior to the Baseline and EOT visits)
    End point type
    Primary
    End point timeframe
    Baseline to end of treatment (16 weeks)
    End point values
    		 Placebo Naltrexone 12 Naltrexone 30 Placebo Non-responder Placebo Placebo Non-responder Naltrexone 12 Placebo Non-responder Naltrexone 30
    Number of subjects analysed
    205
    46
    53
    22
    34
    30
    Units: 1
        Yes
    103
    25
    26
    4
    6
    8
        No
    102
    21
    27
    18
    28
    22
    Statistical analysis title
    		 Combined Logistic regression model Placebo-NTX 12
    Statistical analysis description
    A logistic regression model was used, with treatment (NTX 30 mg/ml, NTX 12 mg/ml, and placebo), the stratification factors at randomisation (EtG of less than 500 ng/ml [abstinent] and nicotine use in the prior week), and the baseline value of WHO Drinking Risk Level as a predictor in the model. The results are presented using model-based estimates of the odd ratios of each active treatment group versus the placebo group with corresponding 95% confidence intervals (CIs) and P values.
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 12 v Placebo v Naltrexone 12
    Number of subjects included in analysis
    307
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9204 [1]
    Method
    		 Regression, Logistic
    Confidence interval
    Notes
    [1] - Combined p-value for Stage I and Stage II
    Statistical analysis title
    		 Combined Logistic regression model Placebo-NTX 30
    Statistical analysis description
    A logistic regression model was used, with treatment (NTX 30 mg/ml, NTX 12 mg/ml, and placebo), the stratification factors at randomisation (EtG of less than 500 ng/ml [abstinent] and nicotine use in the prior week), and the baseline value of WHO Drinking Risk Level as a predictor in the model. The results are presented using model-based estimates of the odd ratios of each active treatment group versus the placebo group with corresponding 95% confidence intervals (CIs) and P values.
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 30 v Placebo v Naltrexone 30
    Number of subjects included in analysis
    310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9289
    Method
    		 Regression, Logistic
    Confidence interval

    Secondary: Time to a 2-level risk reduction

    		 Close Top of page
    End point title
    		 Time to a 2-level risk reduction
    End point description
    Time to a 2-level risk reduction in WHO Drinking Risk Level that is maintained until the EOT
    End point type
    Secondary
    End point timeframe
    Baseline until end of treatment
    End point values
    		 Placebo Naltrexone 12 Naltrexone 30
    Number of subjects analysed
    206
    47
    30
    Units: day
        median (full range (min-max))
    57 (1 to 92)
    57 (1 to 61)
    57 (10 to 65)
    No statistical analyses for this end point

    Secondary: Subjects with No Heavy Drinking Days

    		 Close Top of page
    End point title
    		 Subjects with No Heavy Drinking Days
    End point description
    Proportion of subjects with No Heavy Drinking days, by month
    End point type
    Secondary
    End point timeframe
    Baseline to End of Treatment
    End point values
    		 Placebo Naltrexone 12 Naltrexone 30 Placebo Non-responder Placebo Placebo Non-responder Naltrexone 12 Placebo Non-responder Naltrexone 30
    Number of subjects analysed
    205
    46
    53
    22
    34
    30
    Units: 1
        Yes
    51
    17
    12
    4
    7
    3
        No
    154
    29
    41
    18
    27
    27
    Statistical analysis title
    		 Combined Logistic regression model Placebo-NTX 12
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 12 v Placebo v Naltrexone 12
    Number of subjects included in analysis
    307
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4108 [2]
    Method
    		 Regression, Linear
    Confidence interval
    Notes
    [2] - Combined p-value for Stage I and Stage II
    Statistical analysis title
    		 Combined Logistic regression model Placebo-NTX 30
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 30 v Placebo v Naltrexone 30
    Number of subjects included in analysis
    310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1763 [3]
    Method
    		 Regression, Linear
    Confidence interval
    Notes
    [3] - Combined p-value for Stage I and Stage II

    Secondary: Heavy Drinking Days per Month

    		 Close Top of page
    End point title
    		 Heavy Drinking Days per Month
    End point description
    Percentage heavy drinking days, by month
    End point type
    Secondary
    End point timeframe
    Baseline to End of Treatment
    End point values
    		 Placebo Naltrexone 12 Naltrexone 30 Placebo Non-responder Placebo Placebo Non-responder Naltrexone 12 Placebo Non-responder Naltrexone 30
    Number of subjects analysed
    205
    46
    53
    22
    34
    30
    Units: day
        least squares mean (confidence interval 95%)
    9.75 (8.50 to 10.99)
    7.15 (4.48 to 9.81)
    9.02 (6.64 to 11.39)
    13.61 (10.77 to 16.46)
    11.68 (9.57 to 13.79)
    11.21 (8.82 to 13.59)
    Statistical analysis title
    		 Combined ANCOVA Placebo-NTX 12
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 12 v Placebo v Naltrexone 12
    Number of subjects included in analysis
    307
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0508 [4]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [4] - Combined p-value for Stage I and Stage II
    Statistical analysis title
    		 Combined ANCOVA Placebo-NTX 30
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 30 v Placebo v Naltrexone 30
    Number of subjects included in analysis
    310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.153 [5]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [5] - Combined p-value for Stage I and Stage II

    Secondary: Consecutive Days of Abstinence

    		 Close Top of page
    End point title
    		 Consecutive Days of Abstinence
    End point description
    Number of consecutive days abstinent during treatment, by month
    End point type
    Secondary
    End point timeframe
    Baseline to End of Treatment
    End point values
    		 Placebo Naltrexone 12 Naltrexone 30 Placebo Non-responder Placebo Placebo Non-responder Naltrexone 12 Placebo Non-responder Naltrexone 30
    Number of subjects analysed
    205
    46
    53
    22
    34
    30
    Units: day
        least squares mean (confidence interval 95%)
    4.54 (3.61 to 5.46)
    5.11 (3.10 to 7.12)
    4.50 (2.72 to 6.27)
    3.12 (1.03 to 5.21)
    3.41 (1.79 to 5.03)
    2.62 (0.88 to 4.35)
    Statistical analysis title
    		 Combined ANCOVA Placebo-NTX 12
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 12 v Placebo v Naltrexone 12
    Number of subjects included in analysis
    307
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.486 [6]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [6] - Combined p-value for Stage I and Stage II
    Statistical analysis title
    		 Combined ANCOVA Placebo-NTX 30
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 30 v Placebo v Naltrexone 30
    Number of subjects included in analysis
    310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9737 [7]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [7] - Combined p-value for Stage I and Stage II

    Secondary: Mean Total Alcohol Grams per Day

    		 Close Top of page
    End point title
    		 Mean Total Alcohol Grams per Day
    End point description
    Mean total alcohol grams per day, by month
    End point type
    Secondary
    End point timeframe
    Baseline to End of Treatment
    End point values
    		 Placebo Naltrexone 12 Naltrexone 30 Placebo Non-responder Placebo Placebo Non-responder Naltrexone 12 Placebo Non-responder Naltrexone 30
    Number of subjects analysed
    205
    46
    53
    22
    34
    30
    Units: alcohol grams per day
        least squares mean (confidence interval 95%)
    52.99 (47.78 to 58.20)
    44.65 (33.82 to 55.47)
    45.64 (35.64 to 55.64)
    62.53 (53.03 to 72.04)
    58.47 (51.21 to 65.73)
    56.82 (48.85 to 64.78)
    Statistical analysis title
    		 Combined ANCOVA Placebo-NTX 12
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 12 v Placebo v Naltrexone 12
    Number of subjects included in analysis
    307
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2083 [8]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [8] - Combined p-value for Stage I and Stage II
    Statistical analysis title
    		 Combined ANCOVA Placebo-NTX 30
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 30 v Placebo v Naltrexone 30
    Number of subjects included in analysis
    310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0463 [9]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [9] - Combined p-value for Stage I and Stage II

    Secondary: Drinking Days per Month

    		 Close Top of page
    End point title
    		 Drinking Days per Month
    End point description
    Percentage of drinking days, by month
    End point type
    Secondary
    End point timeframe
    Baseline to End of Treatment
    End point values
    		 Placebo Naltrexone 12 Naltrexone 30 Placebo Non-responder Placebo Placebo Non-responder Naltrexone 12 Placebo Non-responder Naltrexone 30
    Number of subjects analysed
    205
    46
    53
    22
    34
    30
    Units: day
        least squares mean (confidence interval 95%)
    19.00 (17.89 to 20.12)
    17.18 (14.82 to 19.54)
    17.48 (15.33 to 19.62)
    21.68 (19.33 to 24.03)
    20.66 (18.91 to 22.40)
    22.57 (20.63 to 24.52)
    Statistical analysis title
    		 Combined ANCOVA Placebo-NTX 12
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 12 v Naltrexone 12 v Placebo
    Number of subjects included in analysis
    307
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.255 [10]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [10] - Combined p-value for Stage I and Stage II
    Statistical analysis title
    		 Combined ANCOVA Placebo-NTX 30
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 30 v Placebo v Naltrexone 30
    Number of subjects included in analysis
    310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4184 [11]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [11] - Combined p-value for Stage I and Stage II

    Secondary: 1-level reduction in WHO Drinking Risk Level

    		 Close Top of page
    End point title
    		 1-level reduction in WHO Drinking Risk Level
    End point description
    The proportion of subjects showing an improvement in WHO Drinking Risk Level consisting of a 1-level reduction from Baseline to EOT
    End point type
    Secondary
    End point timeframe
    Baseline to End of Treatment
    End point values
    		 Placebo Naltrexone 12 Naltrexone 30 Placebo Non-responder Placebo Placebo Non-responder Naltrexone 12 Placebo Non-responder Naltrexone 30
    Number of subjects analysed
    205
    46
    53
    22
    34
    30
    Units: 1
        Yes
    150
    37
    42
    7
    22
    20
        No
    55
    9
    11
    15
    12
    10
    Statistical analysis title
    		 Combined Logistic regression model Placebo-NTX 12
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 12 v Placebo v Naltrexone 12
    Number of subjects included in analysis
    307
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0169 [12]
    Method
    		 Regression, Logistic
    Confidence interval
    Notes
    [12] - Combined p-value for Stage I and Stage II
    Statistical analysis title
    		 Combined Logistic regression model Placebo-NTX 30
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 30 v Placebo v Naltrexone 30
    Number of subjects included in analysis
    310
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0338 [13]
    Method
    		 Regression, Logistic
    Confidence interval
    Notes
    [13] - Combined p-value for Stage I and Stage II

    Secondary: Alcohol Craving

    		 Close Top of page
    End point title
    		 Alcohol Craving
    End point description
    Alcohol craving by month (Mini Alcohol Craving Experience Questionnaire)
    End point type
    Secondary
    End point timeframe
    Baseline to End of Treatment
    End point values
    		 Placebo Naltrexone 12 Naltrexone 30 Placebo Non-responder Placebo Placebo Non-responder Naltrexone 12 Placebo Non-responder Naltrexone 30
    Number of subjects analysed
    187
    41
    46
    8
    15
    20
    Units: MACE score
        least squares mean (confidence interval 95%)
    15.88 (14.40 to 17.35)
    12.56 (9.41 to 15.71)
    16.57 (13.67 to 19.48)
    9.49 (4.83 to 14.15)
    9.97 (5.73 to 14.22)
    11.56 (8.40 to 14.72)
    Statistical analysis title
    		 Combined ANCOVA Placebo-NTX 12
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 12 v Placebo v Naltrexone 12
    Number of subjects included in analysis
    251
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0339 [14]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [14] - Combined p-value for Stage I and Stage II
    Statistical analysis title
    		 Combined ANCOVA Placebo-NTX 30
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 30 v Placebo v Naltrexone 30
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8769 [15]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [15] - Combined p-value for Stage I and Stage II

    Secondary: Nicotine use

    		 Close Top of page
    End point title
    		 Nicotine use
    End point description
    Change in nicotine use from Baseline to Week 16
    End point type
    Secondary
    End point timeframe
    Baseline to End of Treatment
    End point values
    		 Placebo Naltrexone 12 Naltrexone 30 Placebo Non-responder Placebo Placebo Non-responder Naltrexone 12 Placebo Non-responder Naltrexone 30
    Number of subjects analysed
    91
    23
    20
    9
    15
    13
    Units: mg
        arithmetic mean (standard deviation)
    -6 ± 24.06
    -7.1 ± 40.99
    -1.5 ± 12.44
    1.1 ± 3.38
    0 ± 0
    0 ± 0
    No statistical analyses for this end point

    Secondary: Positive and Negative Affect Scale

    		 Close Top of page
    End point title
    		 Positive and Negative Affect Scale
    End point description
    Positive Affect scores by month
    End point type
    Secondary
    End point timeframe
    Baseline to End of Treatment
    End point values
    		 Placebo Naltrexone 12 Naltrexone 30 Placebo Non-responder Placebo Placebo Non-responder Naltrexone 12 Placebo Non-responder Naltrexone 30
    Number of subjects analysed
    187
    41
    46
    8
    15
    20
    Units: PANAS score
        least squares mean (confidence interval 95%)
    28.01 (27.04 to 28.98)
    29.27 (27.12 to 31.42)
    27.65 (25.70 to 29.53)
    23.47 (18.90 to 28.04)
    28.03 (24.20 to 31.85)
    27.38 (24.15 to 30.61)
    Statistical analysis title
    		 Combined ANCOVA Placebo-NTX 12
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 12 v Placebo v Naltrexone 12
    Number of subjects included in analysis
    251
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.087 [16]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [16] - Combined p-value for Stage I and Stage II
    Statistical analysis title
    		 Combined ANCOVA Placebo-NTX 30
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 30 v Placebo v Naltrexone 30
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6596 [17]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [17] - Combined p-value for Stage I and Stage II

    Secondary: Positive and Negative Affect Scale

    		 Close Top of page
    End point title
    		 Positive and Negative Affect Scale
    End point description
    Negative Affect score
    End point type
    Secondary
    End point timeframe
    Baseline to End of Treatment
    End point values
    		 Placebo Naltrexone 12 Naltrexone 30 Placebo Non-responder Placebo Placebo Non-responder Naltrexone 12 Placebo Non-responder Naltrexone 30
    Number of subjects analysed
    187
    41
    46
    8
    15
    20
    Units: PANAS score
        least squares mean (confidence interval 95%)
    17.82 (16.93 to 18.71)
    17.07 (15.19 to 18.96)
    18.58 (16.82 to 20.33)
    18.28 (13.65 to 22.91)
    13.91 (9.71 to 18.10)
    15.06 (11.88 to 18.23)
    Statistical analysis title
    		 Combined ANCOVA Placebo-NTX 12
    Comparison groups
    Placebo Non-responder Naltrexone 12 v Placebo v Naltrexone 12 v Placebo Non-responder Placebo
    Number of subjects included in analysis
    251
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1196 [18]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [18] - Combined p-value for Stage I and Stage II
    Statistical analysis title
    		 Combined ANCOVA Placebo-NTX 30
    Comparison groups
    Placebo Non-responder Placebo v Placebo Non-responder Naltrexone 30 v Placebo v Naltrexone 30
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5893 [19]
    Method
    		 ANCOVA
    Confidence interval
    Notes
    [19] - Combined p-value for Stage I and Stage II

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    18 Jan 2022 - 14 Feb 2023
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    Placebo + Placebo - Stage I
    Reporting group description
    		 -

    Reporting group title
    Placebo + Placebo - Stage II
    Reporting group description
    		 -

    Reporting group title
    Placebo + NTX 12 - Stage I
    Reporting group description
    		 -

    Reporting group title
    Placebo + NTX 12 - Stage II
    Reporting group description
    		 -

    Reporting group title
    Placebo + NTX 30 - Stage I
    Reporting group description
    		 -

    Reporting group title
    Placebo + NTX 30 - Stage II
    Reporting group description
    		 -

    Reporting group title
    NTX 12 + NTX 12 - Stage I
    Reporting group description
    		 -

    Reporting group title
    NTX 12 + NTX 12 - Stage II
    Reporting group description
    		 -

    Reporting group title
    NTX 30 + NTX 30 - Stage I
    Reporting group description
    		 -

    Reporting group title
    NTX 30 + NTX 30 - Stage II
    Reporting group description
    		 -

    Serious adverse events
    		 Placebo + Placebo - Stage I Placebo + Placebo - Stage II Placebo + NTX 12 - Stage I Placebo + NTX 12 - Stage II Placebo + NTX 30 - Stage I Placebo + NTX 30 - Stage II NTX 12 + NTX 12 - Stage I NTX 12 + NTX 12 - Stage II NTX 30 + NTX 30 - Stage I NTX 30 + NTX 30 - Stage II
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 142 (0.70%)
    2 / 123 (1.63%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 30 (3.33%)
    1 / 30 (3.33%)
    1 / 47 (2.13%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Injury, poisoning and procedural complications
    Limb traumatic amputation
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fatal accident
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 47 (2.13%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash erythematous
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Binge drinking
         subjects affected / exposed
    1 / 142 (0.70%)
    1 / 123 (0.81%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Behaviour disorder due to a general medical condition
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 123 (0.81%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental disorder due to a general medical condition
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 123 (0.81%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2.5%
    Non-serious adverse events
    		 Placebo + Placebo - Stage I Placebo + Placebo - Stage II Placebo + NTX 12 - Stage I Placebo + NTX 12 - Stage II Placebo + NTX 30 - Stage I Placebo + NTX 30 - Stage II NTX 12 + NTX 12 - Stage I NTX 12 + NTX 12 - Stage II NTX 30 + NTX 30 - Stage I NTX 30 + NTX 30 - Stage II
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    57 / 142 (40.14%)
    28 / 123 (22.76%)
    12 / 34 (35.29%)
    9 / 34 (26.47%)
    13 / 30 (43.33%)
    9 / 30 (30.00%)
    23 / 47 (48.94%)
    9 / 41 (21.95%)
    28 / 53 (52.83%)
    14 / 46 (30.43%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    4 / 142 (2.82%)
    2 / 123 (1.63%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    1 / 47 (2.13%)
    0 / 41 (0.00%)
    1 / 53 (1.89%)
    1 / 46 (2.17%)
         occurrences all number
    4
    3
    0
    0
    1
    0
    1
    0
    1
    1
    Surgical and medical procedures
    Bone graft
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Dental prosthesis placement
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    3 / 142 (2.11%)
    0 / 123 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    6 / 47 (12.77%)
    0 / 41 (0.00%)
    1 / 53 (1.89%)
    0 / 46 (0.00%)
         occurrences all number
    5
    0
    2
    0
    0
    1
    6
    0
    1
    0
    Asthenia
         subjects affected / exposed
    4 / 142 (2.82%)
    1 / 123 (0.81%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    2 / 30 (6.67%)
    1 / 30 (3.33%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    5
    1
    0
    0
    2
    1
    0
    0
    0
    0
    Chills
         subjects affected / exposed
    1 / 142 (0.70%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Injection site pain
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Malaise
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Pain
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Rhinorrhoea
         subjects affected / exposed
    12 / 142 (8.45%)
    2 / 123 (1.63%)
    4 / 34 (11.76%)
    0 / 34 (0.00%)
    2 / 30 (6.67%)
    0 / 30 (0.00%)
    4 / 47 (8.51%)
    1 / 41 (2.44%)
    10 / 53 (18.87%)
    2 / 46 (4.35%)
         occurrences all number
    16
    2
    4
    0
    3
    0
    4
    1
    16
    2
    Nasal discomfort
         subjects affected / exposed
    12 / 142 (8.45%)
    2 / 123 (1.63%)
    2 / 34 (5.88%)
    0 / 34 (0.00%)
    4 / 30 (13.33%)
    4 / 30 (13.33%)
    5 / 47 (10.64%)
    0 / 41 (0.00%)
    5 / 53 (9.43%)
    2 / 46 (4.35%)
         occurrences all number
    21
    3
    3
    0
    15
    4
    6
    0
    7
    2
    Nasal inflammation
         subjects affected / exposed
    3 / 142 (2.11%)
    1 / 123 (0.81%)
    2 / 34 (5.88%)
    1 / 34 (2.94%)
    2 / 30 (6.67%)
    2 / 30 (6.67%)
    5 / 47 (10.64%)
    0 / 41 (0.00%)
    1 / 53 (1.89%)
    0 / 46 (0.00%)
         occurrences all number
    4
    1
    2
    2
    3
    2
    6
    0
    1
    0
    Sneezing
         subjects affected / exposed
    5 / 142 (3.52%)
    3 / 123 (2.44%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 47 (2.13%)
    0 / 41 (0.00%)
    3 / 53 (5.66%)
    1 / 46 (2.17%)
         occurrences all number
    11
    6
    1
    0
    0
    0
    1
    0
    4
    1
    Epistaxis
         subjects affected / exposed
    2 / 142 (1.41%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    3 / 47 (6.38%)
    0 / 41 (0.00%)
    2 / 53 (3.77%)
    1 / 46 (2.17%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    3
    0
    2
    2
    Nasal congestion
         subjects affected / exposed
    2 / 142 (1.41%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    2 / 30 (6.67%)
    0 / 30 (0.00%)
    1 / 47 (2.13%)
    1 / 41 (2.44%)
    2 / 53 (3.77%)
    1 / 46 (2.17%)
         occurrences all number
    2
    0
    0
    0
    7
    0
    1
    1
    4
    1
    Rhinalgia
         subjects affected / exposed
    1 / 142 (0.70%)
    1 / 123 (0.81%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 47 (2.13%)
    0 / 41 (0.00%)
    3 / 53 (5.66%)
    2 / 46 (4.35%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    1
    0
    4
    2
    Oropharyngeal pain
         subjects affected / exposed
    1 / 142 (0.70%)
    2 / 123 (1.63%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 30 (3.33%)
    2 / 30 (6.67%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    2
    0
    0
    1
    2
    0
    0
    0
    0
    Cough
         subjects affected / exposed
    3 / 142 (2.11%)
    3 / 123 (2.44%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    1 / 53 (1.89%)
    0 / 46 (0.00%)
         occurrences all number
    3
    4
    0
    0
    1
    0
    0
    0
    2
    0
    Nasal pruritus
         subjects affected / exposed
    3 / 142 (2.11%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    1 / 47 (2.13%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    3
    0
    0
    0
    1
    0
    1
    0
    0
    0
    Throat irritation
         subjects affected / exposed
    3 / 142 (2.11%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    4
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Intranasal paraesthesia
         subjects affected / exposed
    1 / 142 (0.70%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 30 (3.33%)
    1 / 30 (3.33%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    1
    0
    0
    0
    0
    Hyperactive pharyngeal reflex
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 47 (2.13%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    10 / 142 (7.04%)
    1 / 123 (0.81%)
    2 / 34 (5.88%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    2 / 53 (3.77%)
    0 / 46 (0.00%)
         occurrences all number
    13
    1
    2
    0
    0
    0
    0
    0
    3
    0
    Sleep disorder
         subjects affected / exposed
    3 / 142 (2.11%)
    2 / 123 (1.63%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    2 / 53 (3.77%)
    0 / 46 (0.00%)
         occurrences all number
    3
    2
    0
    0
    1
    0
    0
    0
    3
    0
    Anxiety
         subjects affected / exposed
    2 / 142 (1.41%)
    1 / 123 (0.81%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    2 / 53 (3.77%)
    0 / 46 (0.00%)
         occurrences all number
    4
    5
    0
    0
    0
    0
    0
    0
    2
    0
    Claustrophobia
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Depersonalisation/derealisation disorder
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Alcohol withdrawal syndrome
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Depressed mood
         subjects affected / exposed
    2 / 142 (1.41%)
    1 / 123 (0.81%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 47 (2.13%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    3
    1
    1
    0
    0
    0
    1
    0
    0
    0
    Product issues
    Product taste abnormal
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 30 (3.33%)
    3 / 30 (10.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    1 / 53 (1.89%)
    1 / 46 (2.17%)
         occurrences all number
    0
    0
    0
    0
    1
    3
    0
    0
    2
    1
    Injury, poisoning and procedural complications
    Joint injury
         subjects affected / exposed
    1 / 142 (0.70%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    20 / 142 (14.08%)
    6 / 123 (4.88%)
    5 / 34 (14.71%)
    1 / 34 (2.94%)
    4 / 30 (13.33%)
    1 / 30 (3.33%)
    6 / 47 (12.77%)
    2 / 41 (4.88%)
    10 / 53 (18.87%)
    3 / 46 (6.52%)
         occurrences all number
    45
    12
    6
    1
    7
    1
    6
    2
    16
    3
    Dizziness
         subjects affected / exposed
    4 / 142 (2.82%)
    2 / 123 (1.63%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    6 / 47 (12.77%)
    1 / 41 (2.44%)
    3 / 53 (5.66%)
    0 / 46 (0.00%)
         occurrences all number
    5
    2
    0
    0
    0
    0
    8
    1
    8
    0
    Somnolence
         subjects affected / exposed
    5 / 142 (3.52%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    2 / 47 (4.26%)
    0 / 41 (0.00%)
    3 / 53 (5.66%)
    0 / 46 (0.00%)
         occurrences all number
    6
    0
    0
    0
    2
    0
    2
    0
    6
    0
    Neuralgia
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Ear and labyrinth disorders
    Ear congestion
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Eye disorders
    Lacrimation increased
         subjects affected / exposed
    2 / 142 (1.41%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    1 / 47 (2.13%)
    0 / 41 (0.00%)
    2 / 53 (3.77%)
    1 / 46 (2.17%)
         occurrences all number
    3
    0
    0
    0
    3
    0
    1
    0
    3
    1
    Eye pruritus
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    4 / 142 (2.82%)
    0 / 123 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    2 / 30 (6.67%)
    0 / 47 (0.00%)
    2 / 41 (4.88%)
    3 / 53 (5.66%)
    2 / 46 (4.35%)
         occurrences all number
    6
    0
    1
    0
    0
    3
    0
    2
    5
    2
    Abdominal pain
         subjects affected / exposed
    1 / 142 (0.70%)
    0 / 123 (0.00%)
    2 / 34 (5.88%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    1 / 53 (1.89%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    4
    0
    0
    0
    0
    0
    3
    0
    Diarrhoea
         subjects affected / exposed
    3 / 142 (2.11%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 30 (3.33%)
    1 / 30 (3.33%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    2 / 53 (3.77%)
    1 / 46 (2.17%)
         occurrences all number
    5
    0
    0
    0
    1
    1
    0
    0
    2
    1
    Toothache
         subjects affected / exposed
    5 / 142 (3.52%)
    1 / 123 (0.81%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    1 / 41 (2.44%)
    1 / 53 (1.89%)
    0 / 46 (0.00%)
         occurrences all number
    8
    2
    0
    0
    0
    0
    0
    1
    2
    0
    Dry mouth
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    1 / 53 (1.89%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    Paraesthesia oral
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Crohn's disease
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    2 / 142 (1.41%)
    1 / 123 (0.81%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    1 / 53 (1.89%)
    0 / 46 (0.00%)
         occurrences all number
    2
    1
    0
    1
    0
    0
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Hyperhidrosis
         subjects affected / exposed
    1 / 142 (0.70%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    1 / 47 (2.13%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    2
    0
    0
    0
    Eczema
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    3 / 142 (2.11%)
    1 / 123 (0.81%)
    1 / 34 (2.94%)
    3 / 34 (8.82%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    1 / 47 (2.13%)
    0 / 41 (0.00%)
    3 / 53 (5.66%)
    1 / 46 (2.17%)
         occurrences all number
    3
    1
    1
    3
    1
    0
    1
    0
    3
    1
    Pharyngitis
         subjects affected / exposed
    1 / 142 (0.70%)
    1 / 123 (0.81%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 30 (3.33%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    2
    0
    0
    1
    0
    0
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    1 / 47 (2.13%)
    1 / 41 (2.44%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    1
    0
    0
    Rhinitis
         subjects affected / exposed
    1 / 142 (0.70%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    1 / 53 (1.89%)
    1 / 46 (2.17%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    1
    1
    COVID-19
         subjects affected / exposed
    3 / 142 (2.11%)
    1 / 123 (0.81%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 47 (2.13%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    3
    1
    0
    1
    0
    0
    1
    0
    0
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 142 (0.00%)
    1 / 123 (0.81%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    Sinusitis
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 47 (2.13%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    1
    0
    0
    0
    Varicella
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 142 (0.70%)
    1 / 123 (0.81%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    2 / 47 (4.26%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    1 / 46 (2.17%)
         occurrences all number
    2
    1
    0
    0
    0
    1
    2
    0
    0
    1
    Increased appetite
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    2 / 53 (3.77%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    Gout
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    1 / 53 (1.89%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    Alcohol intolerance
         subjects affected / exposed
    0 / 142 (0.00%)
    0 / 123 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 47 (0.00%)
    0 / 41 (0.00%)
    0 / 53 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 Apr 2020
    • Clarified thresholds for Screening liver function test levels • Clarified thresholds for breath alcohol test results
    15 Jun 2022
    • Clarified the WHO Drinking Risk level of High Risk or Very High Risk and its calculation from the TLFB interview • Provided that, in exceptional circumstances and following approval from the Sponsor, the IMP could be dispensed at unscheduled and nondispensing visits • Added subject numbering information • Clarified the requirement for a follow-up call after the Early Withdrawal Visit where possible

    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.
    Randomisation was not conducted per protocol due to an IWRS set-up error. The designed treatment allocation ratio at both stages could not be achieved. This issue was identified during final analysis and a Notification of Serious Breach was reported.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun Apr 28 19:19:26 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA