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   43857   clinical trials with a EudraCT protocol, of which   7284   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:
    PHARMACODYNAMIC EFFECTS OF NICOTINE MOUTH SPRAY AND CYTISINE TABLET. A STUDY IN HEALTHY SMOKERS

    Summary
    EudraCT number
    		 2016-001267-36
    Trial protocol
    		 SE  
    Global end of trial date
    07 Oct 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    26 Jul 2017
    First version publication date
    26 Jul 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CO-160310091324-SCCT
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    McNeil AB
    Sponsor organisation address
    251 09, Helsingborg, Sweden, Box 941
    Public contact
    Global Regulatory Affairs OTC Hsbg, McNeil AB, 46 42288734, GRAREGH@its.jnj.com
    Scientific contact
    Global Regulatory Affairs OTC Hsbg, McNeil AB, 46 42288734, GRAREGH@its.jnj.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
    07 Oct 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Oct 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to compare oromucosal nicotine spray (ONS), two sprays of 1 milligram (mg) nicotine, and one Tabex tablet of 1.5 mg cytisine after 12 hours of overnight abstinence with respect to reduction of urges to smoke during the first 5 minutes after start of treatment and to compare the two treatments with respect to the urges-to-smoke scores at 30, 45, and 60 seconds, 3 and 5 minutes versus baseline.
    Protection of trial subjects
    Safety was evaluated by monitoring of adverse events (AEs) throughout study and, vital signs measurements, physical and other observational examinations was evaluated during screening phase.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 Jun 2016
    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
    Sweden: 61
    Worldwide total number of subjects
    61
    EEA total number of subjects
    61
    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)
    61
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This study was conducted from 27 June 2016 to 07 October 2016 in Sweden.

    Pre-assignment
    Screening details
    		 A total of 61 subjects were enrolled in study out of which 28 were males and 33 were females.

    Period 1
    Period 1 title
    Treatment Period 1
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Sequence 1: Nicorette Oromucosal Nicotine Spray (ONS), Tabex
    Arm description
    		 Subjects received nicorette peppermint oromucosal spray 2 milligram (mg) as two consecutive sprays of unit dose of 1 mg at two separate visits as treatment A followed by tabex tablet 1.5 mg orally with 150 milliliter (mL) of ambient temperature water as treatment B. Each treatment was separated by wash-out periods of at least 36 hours.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tabex
    Investigational medicinal product code
    SUB31171
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received tabex tablet 1.5 mg orally with 150 milliliter (mL) of ambient temperature water as treatment B.

    Investigational medicinal product name
    Nicorette Pepparmint 1 mg/spray
    Investigational medicinal product code
    SUB14645MIG
    Other name
    Pharmaceutical forms
    Oromucosal spray, solution
    Routes of administration
    Oromucosal use
    Dosage and administration details
    Subjects received nicorette peppermint oromucosal spray 2 mg as two consecutive sprays of unit dose of 1 mg at two separate visits as treatment A.

    Arm title
    		 Sequence 2: Tabex, Nicorette ONS
    Arm description
    		 Subjects received tabex tablet 1.5 mg orally with 150 milliliter (mL) of ambient temperature water as treatment B followed by nicorette peppermint oromucosal spray 2 milligram (mg) as two consecutive sprays of unit dose of 1 mg at two separate visits as treatment A. Each treatment was separated by wash-out periods of at least 36 hours.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tabex
    Investigational medicinal product code
    SUB31171
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received tabex tablet 1.5 mg orally with 150 milliliter (mL) of ambient temperature water as treatment B.

    Investigational medicinal product name
    Nicorette Pepparmint 1 mg/spray
    Investigational medicinal product code
    SUB14645MIG
    Other name
    Pharmaceutical forms
    Oromucosal spray, solution
    Routes of administration
    Oromucosal use
    Dosage and administration details
    Subjects received nicorette peppermint oromucosal spray 2 mg as two consecutive sprays of unit dose of 1 mg at two separate visits as treatment A.

    Number of subjects in period 1
    		Sequence 1: Nicorette Oromucosal Nicotine Spray (ONS), Tabex Sequence 2: Tabex, Nicorette ONS
    Started
    31
    30
    Completed
    31
    30
    Period 2
    Period 2 title
    Treatment Period 2
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Sequence 1: Nicorette ONS, Tabex
    Arm description
    		 Subjects received nicorette peppermint oromucosal spray 2 mg as two consecutive sprays of unit dose of 1 mg at two separate visits as treatment A followed by tabex tablet 1.5 mg orally with 150 mL of ambient temperature water as treatment B. Each treatment was separated by wash-out periods of at least 36 hours.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tabex
    Investigational medicinal product code
    SUB31171
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received tabex tablet 1.5 mg orally with 150 milliliter (mL) of ambient temperature water as treatment B.

    Investigational medicinal product name
    Nicorette Pepparmint 1 mg/spray
    Investigational medicinal product code
    SUB14645MIG
    Other name
    Pharmaceutical forms
    Oromucosal spray, solution
    Routes of administration
    Oromucosal use
    Dosage and administration details
    Subjects received nicorette peppermint oromucosal spray 2 mg as two consecutive sprays of unit dose of 1 mg at two separate visits as treatment A.

    Arm title
    		 Sequence 2: Tabex, Nicorette ONS
    Arm description
    		 Subjects received tabex tablet 1.5 mg orally with 150 milliliter (mL) of ambient temperature water as treatment B followed by nicorette peppermint oromucosal spray 2 milligram (mg) as two consecutive sprays of unit dose of 1 mg at two separate visits as treatment A. Each treatment was separated by wash-out periods of at least 36 hours.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nicorette Pepparmint 1 mg/spray
    Investigational medicinal product code
    SUB14645MIG
    Other name
    Pharmaceutical forms
    Oromucosal spray, solution
    Routes of administration
    Oromucosal use
    Dosage and administration details
    Subjects received nicorette peppermint oromucosal spray 2 mg as two consecutive sprays of unit dose of 1 mg at two separate visits as treatment A.

    Investigational medicinal product name
    Tabex
    Investigational medicinal product code
    SUB31171
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received tabex tablet 1.5 mg orally with 150 milliliter (mL) of ambient temperature water as treatment B.

    Number of subjects in period 2
    		Sequence 1: Nicorette ONS, Tabex Sequence 2: Tabex, Nicorette ONS
    Started
    31
    30
    Completed
    26
    28
    Not completed
    5
    2
         Consent withdrawn by subject
    -
    1
         Other
    2
    -
         Lost to follow-up
    3
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Sequence 1: Nicorette Oromucosal Nicotine Spray (ONS), Tabex
    Reporting group description
    		 Subjects received nicorette peppermint oromucosal spray 2 milligram (mg) as two consecutive sprays of unit dose of 1 mg at two separate visits as treatment A followed by tabex tablet 1.5 mg orally with 150 milliliter (mL) of ambient temperature water as treatment B. Each treatment was separated by wash-out periods of at least 36 hours.

    Reporting group title
    Sequence 2: Tabex, Nicorette ONS
    Reporting group description
    		 Subjects received tabex tablet 1.5 mg orally with 150 milliliter (mL) of ambient temperature water as treatment B followed by nicorette peppermint oromucosal spray 2 milligram (mg) as two consecutive sprays of unit dose of 1 mg at two separate visits as treatment A. Each treatment was separated by wash-out periods of at least 36 hours.

    Reporting group values
    		 Sequence 1: Nicorette Oromucosal Nicotine Spray (ONS), Tabex Sequence 2: Tabex, Nicorette ONS Total
    Number of subjects
    		 31 30 61
    Title for AgeCategorical
    Units: subjects
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 31 30 61
        From 65 to 84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Title for AgeContinuous
    Units: years
        arithmetic mean (standard deviation)
    		 33 ± 10.97 31.6 ± 10.85 -
    Title for Gender
    Units: subjects
        Female
    		 15 18 33
        Male
    		 16 12 28

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Sequence 1: Nicorette Oromucosal Nicotine Spray (ONS), Tabex
    Reporting group description
    		 Subjects received nicorette peppermint oromucosal spray 2 milligram (mg) as two consecutive sprays of unit dose of 1 mg at two separate visits as treatment A followed by tabex tablet 1.5 mg orally with 150 milliliter (mL) of ambient temperature water as treatment B. Each treatment was separated by wash-out periods of at least 36 hours.

    Reporting group title
    Sequence 2: Tabex, Nicorette ONS
    Reporting group description
    		 Subjects received tabex tablet 1.5 mg orally with 150 milliliter (mL) of ambient temperature water as treatment B followed by nicorette peppermint oromucosal spray 2 milligram (mg) as two consecutive sprays of unit dose of 1 mg at two separate visits as treatment A. Each treatment was separated by wash-out periods of at least 36 hours.
    Reporting group title
    Sequence 1: Nicorette ONS, Tabex
    Reporting group description
    		 Subjects received nicorette peppermint oromucosal spray 2 mg as two consecutive sprays of unit dose of 1 mg at two separate visits as treatment A followed by tabex tablet 1.5 mg orally with 150 mL of ambient temperature water as treatment B. Each treatment was separated by wash-out periods of at least 36 hours.

    Reporting group title
    Sequence 2: Tabex, Nicorette ONS
    Reporting group description
    		 Subjects received tabex tablet 1.5 mg orally with 150 milliliter (mL) of ambient temperature water as treatment B followed by nicorette peppermint oromucosal spray 2 milligram (mg) as two consecutive sprays of unit dose of 1 mg at two separate visits as treatment A. Each treatment was separated by wash-out periods of at least 36 hours.

    Subject analysis set title
    Nicorette ONS (Treatment A)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All randomized subjects with any efficacy assessments and received nicorette peppermint oromucosal spray 2 milligram (mg) as two consecutive sprays of unit dose of 1 mg at two separate visits.

    Subject analysis set title
    Tabex (Treatment B)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All randomized subjects with any efficacy assessments and received tabex tablet 1.5 mg orally with 150 milliliter (mL) of ambient temperature water.

    Subject analysis set title
    ONS Versus (vs.) Tabex
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All randomized subjects with any efficacy assessments and involved in comparisons of ONS vs. Tabex with respect to time to reduce craving score.

    Primary: Average Change in Visual Analog Scale (VAS) Craving Score Compared to Baseline

    		 Close Top of page
    End point title
    		 Average Change in Visual Analog Scale (VAS) Craving Score Compared to Baseline
    End point description
    Urges to smoke was scored on a 100 millimeter (mm) VAS before treatment and then repeatedly during 2 hours. Baseline urges to smoke was also rated using a 4- grade scale. On the scale, 0 corresponds to “no urge to smoke” and 100 mm corresponds to “extreme urge to smoke”. Full analysis set population included all randomized subjects with any efficacy assessments.
    End point type
    Primary
    End point timeframe
    Baseline, 30 seconds (sec), 45 sec, 1 minute (min), 3 min and 5 min
    End point values
    		 Nicorette ONS (Treatment A) Tabex (Treatment B)
    Number of subjects analysed
    58
    56
    Units: millimeter
    arithmetic mean (standard deviation)
        30 seconds (sec)
    -8 ± 9.8
    -0.8 ± 4.9
        45 sec
    -11.8 ± 14.1
    -1 ± 6.1
        1 minute (min)
    -14.7 ± 16.5
    -1.3 ± 6
        3 min
    -23 ± 21
    -3.8 ± 9.7
        5 min
    -26.3 ± 22
    -5.8 ± 12
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Analysis was done for average change in VAS craving score compared to baseline up to 30 seconds. Treatment comparison was based on a mixed linear model including sequence, treatment and period as fixed effects and subject, nested within sequence, as random effect. Additionally, the baseline urges-to-smoke score at time zero, was calculated as an average of the three pretreatment urge assessments, was included as a co-varying fixed effect.
    Comparison groups
    Tabex (Treatment B) v Nicorette ONS (Treatment A)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.8
         upper limit
    		 -4.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.4
    Notes
    [1] - 58 subjects from treatment A and 56 subjects from treatment B were involved in the analysis (Cross over design with random model). In total 61 unique subjects were included in the analysis.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Analysis was done for average change in VAS craving score compared to baseline up to 45 seconds. Treatment comparison was based on a mixed linear model including sequence, treatment and period as fixed effects and subject, nested within sequence, as random effect. Additionally, the baseline urges-to-smoke score at time zero, was calculated as an average of the three pretreatment urge assessments, was included as a co-varying fixed effect.
    Comparison groups
    Nicorette ONS (Treatment A) v Tabex (Treatment B)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -10.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.5
         upper limit
    		 -6.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    2
    Notes
    [2] - 58 subjects from treatment A and 56 subjects from treatment B were involved in the analysis (Cross over design with random model). In total 61 unique subjects were included in the analysis.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Analysis was done for average change in VAS craving score compared to baseline up to 1 minute. Treatment comparison was based on a mixed linear model including sequence, treatment and period as fixed effects and subject, nested within sequence, as random effect. Additionally, the baseline urges-to-smoke score at time zero, was calculated as an average of the three pretreatment urge assessments, was included as a co-varying fixed effect.
    Comparison groups
    Tabex (Treatment B) v Nicorette ONS (Treatment A)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -13.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.6
         upper limit
    		 -8.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.2
    Notes
    [3] - 58 subjects from treatment A and 56 subjects from treatment B were involved in the analysis (Cross over design with random model). In total 61 unique subjects were included in the analysis.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    Analysis was done for average change in VAS craving score compared to baseline up to 3 minutes. Treatment comparison was based on a mixed linear model including sequence, treatment and period as fixed effects and subject, nested within sequence, as random effect. Additionally, the baseline urges-to-smoke score at time zero, was calculated as an average of the three pretreatment urge assessments, was included as a co-varying fixed effect.
    Comparison groups
    Nicorette ONS (Treatment A) v Tabex (Treatment B)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [4]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -18.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24
         upper limit
    		 -13.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.7
    Notes
    [4] - 58 subjects from treatment A and 56 subjects from treatment B were involved in the analysis (Cross over design with random model). In total 61 unique subjects were included in the analysis.
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    Analysis was done for average change in VAS craving score compared to baseline up to 5 minutes. Treatment comparison was based on a mixed linear model including sequence, treatment and period as fixed effects and subject, nested within sequence, as random effect. Additionally, the baseline urges-to-smoke score at time zero, was calculated as an average of the three pretreatment urge assessments, was included as a co-varying fixed effect.
    Comparison groups
    Nicorette ONS (Treatment A) v Tabex (Treatment B)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -19.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25.3
         upper limit
    		 -14.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.7
    Notes
    [5] - 58 subjects from treatment A and 56 subjects from treatment B were involved in the analysis (Cross over design with random model). In total 61 unique subjects were included in the analysis.

    Primary: Change in VAS Craving Score Compared to Baseline

    		 Close Top of page
    End point title
    		 Change in VAS Craving Score Compared to Baseline
    End point description
    Urges to smoke was scored on a 100 millimeter (mm) VAS before treatment and then repeatedly during 2 hours. Baseline urges to smoke was also rated using a 4- grade scale. On the scale, 0 corresponds to “no urge to smoke” and 100 mm corresponds to “extreme urge to smoke”. Full analysis set population included all randomized subjects with any efficacy assessments.
    End point type
    Primary
    End point timeframe
    Baseline, 30 seconds (sec), 45 sec, 1 minute (min), 3 min and 5 min
    End point values
    		 Nicorette ONS (Treatment A) Tabex (Treatment B)
    Number of subjects analysed
    58
    56
    Units: millimeter
    arithmetic mean (standard deviation)
        30 sec
    -15.9 ± 19.5
    -1.5 ± 9.7
        45 sec
    -21.9 ± 23.9
    -1.6 ± 8.2
        1 min
    -24.5 ± 24.2
    -2.8 ± 10.6
        3 min
    -30.3 ± 25.9
    -6.8 ± 14.6
        5 min
    -34.3 ± 26
    -10.7 ± 18
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Analysis was done for change in VAS craving score compared to baseline at 30 seconds. Treatment comparison was based on a mixed linear model including sequence, treatment and period as fixed effects and subject, nested within sequence, as random effect. Additionally, the baseline urges-to-smoke score at time zero, was calculated as an average of the three pretreatment urge assessments, was included as a co-varying fixed effect.
    Comparison groups
    Nicorette ONS (Treatment A) v Tabex (Treatment B)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -19.7
         upper limit
    		 -8.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.8
    Notes
    [6] - 58 subjects from treatment A and 56 subjects from treatment B were involved in the analysis (Cross over design with random model). In total 61 unique subjects were included in the analysis.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Analysis was done for change in VAS craving score compared to baseline at 45 seconds. Treatment comparison was based on a mixed linear model including sequence, treatment and period as fixed effects and subject, nested within sequence, as random effect. Additionally, the baseline urges-to-smoke score at time zero, was calculated as an average of the three pretreatment urge assessments, was included as a co-varying fixed effect.
    Comparison groups
    Nicorette ONS (Treatment A) v Tabex (Treatment B)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -20
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.4
         upper limit
    		 -13.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.2
    Notes
    [7] - 58 subjects from treatment A and 56 subjects from treatment B were involved in the analysis (Cross over design with random model). In total 61 unique subjects were included in the analysis.
    Statistical analysis title
    		 Statistical analysis 3
    Statistical analysis description
    Analysis was done for change in VAS craving score compared to baseline at 1 minute. Treatment comparison was based on a mixed linear model including sequence, treatment and period as fixed effects and subject, nested within sequence, as random effect. Additionally, the baseline urges-to-smoke score at time zero, was calculated as an average of the three pretreatment urge assessments, was included as a co-varying fixed effect.
    Comparison groups
    Nicorette ONS (Treatment A) v Tabex (Treatment B)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [8]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Median difference (final values)
    Point estimate
    -21.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.7
         upper limit
    		 -14.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.2
    Notes
    [8] - 58 subjects from treatment A and 56 subjects from treatment B were involved in the analysis (Cross over design with random model). In total 61 unique subjects were included in the analysis.
    Statistical analysis title
    		 Statistical analysis 4
    Statistical analysis description
    Analysis was done for change in VAS craving score compared to baseline at 3 minutes. Treatment comparison was based on a mixed linear model including sequence, treatment and period as fixed effects and subject, nested within sequence, as random effect. Additionally, the baseline urges-to-smoke score at time zero, was calculated as an average of the three pretreatment urge assessments, was included as a co-varying fixed effect.
    Comparison groups
    Nicorette ONS (Treatment A) v Tabex (Treatment B)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -22.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.7
         upper limit
    		 -16.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.1
    Notes
    [9] - 58 subjects from treatment A and 56 subjects from treatment B were involved in the analysis (Cross over design with random model). In total 61 unique subjects were included in the analysis.
    Statistical analysis title
    		 Statistical analysis 5
    Statistical analysis description
    Analysis was done for change in VAS craving score compared to baseline at 5 minutes. Treatment comparison was based on a mixed linear model including sequence, treatment and period as fixed effects and subject, nested within sequence, as random effect. Additionally, the baseline urges-to-smoke score at time zero, was calculated as an average of the three pretreatment urge assessments, was included as a co-varying fixed effect.
    Comparison groups
    Nicorette ONS (Treatment A) v Tabex (Treatment B)
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [10]
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -22.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.4
         upper limit
    		 -16.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.1
    Notes
    [10] - 58 subjects from treatment A and 56 subjects from treatment B were involved in the analysis (Cross over design with random model). In total 61 unique subjects were included in the analysis.

    Secondary: Time to a 25 Percent (%) Reduction From Baseline Intensity of Urges to Smoke Score

    		 Close Top of page
    End point title
    		 Time to a 25 Percent (%) Reduction From Baseline Intensity of Urges to Smoke Score
    End point description
    Kaplan-Meier survival estimates method was used for the time to 25% reduction in urges to smoke. Full analysis set population included all randomized subjects with any efficacy assessments. Here '99999' represents that no estimate was available for median and confidence interval for this specific outcome result.
    End point type
    Secondary
    End point timeframe
    up to 2 hours
    End point values
    		 Nicorette ONS (Treatment A) Tabex (Treatment B)
    Number of subjects analysed
    58
    56
    Units: Minutes
    median (confidence interval 95%)
        25 % quartiles
    0.245 (0.195 to 0.356)
    3.085 (1.274 to 7.871)
        50 % quartiles
    0.707 (0.378 to 2.142)
    16.51 (7.871 to 44.46)
        75 % quartiles
    3.183 (2.142 to 12.97)
    99999 (69.37 to 99999)
    No statistical analyses for this end point

    Secondary: Rating of Withdrawal Symptoms

    		 Close Top of page
    End point title
    		 Rating of Withdrawal Symptoms
    End point description
    The four negative affect related items of the Minnesota Nicotine Withdrawal Scale (MNWS) were used. These include depressed mood, irritability, anxiety, and difficulty concentrating. Each was rated on a 5-grade scale; 0 – not present, 1 – slight, 2 – mild, 3 – moderate, 4 – severe within 10 minutes before treatment and at 5 and 30 minutes, as well as 1 and 2 hours after treatment. Full analysis set population included all randomized subjects with any efficacy assessments.
    End point type
    Secondary
    End point timeframe
    Baseline, 5 min, 30 min, 1 hour and 2 hour
    End point values
    		 Nicorette ONS (Treatment A) Tabex (Treatment B)
    Number of subjects analysed
    59
    56
    Units: Unit on a scale
    arithmetic mean (standard deviation)
        Depressed Mood: Baseline
    1.6 ± 1.1
    1.6 ± 1
        Depressed Mood: 5 min
    1.1 ± 1
    1.1 ± 0.9
        Depressed Mood: 30 min
    1 ± 1
    0.9 ± 1
        Depressed Mood: 1 hour
    0.9 ± 1
    0.8 ± 0.9
        Depressed Mood: 2 hour
    0.9 ± 0.9
    0.9 ± 1
        Irritability: Baseline
    1.8 ± 1.2
    1.7 ± 1.2
        Irritability: 5 min
    1.3 ± 1.1
    1.3 ± 1.1
        Irritability: 30 min
    1 ± 1
    1.1 ± 1.1
        Irritability: 1 hour
    0.9 ± 1
    1.1 ± 1.1
        Irritability: 2 hour
    1.1 ± 1
    1 ± 1
        Anxiety: Baseline
    1.4 ± 1.1
    1.2 ± 1.1
        Anxiety: 5 min
    0.9 ± 0.9
    0.8 ± 0.9
        Anxiety: 30 min
    0.8 ± 0.9
    0.8 ± 0.8
        Anxiety: 1 hour
    0.8 ± 0.9
    0.9 ± 1
        Anxiety: 2 hour
    0.9 ± 1
    0.9 ± 1
        Difficulty Concentrating: Baseline
    1.8 ± 1.2
    1.6 ± 1.2
        Difficulty Concentrating: 5 min
    1.2 ± 1.1
    1.3 ± 1.1
        Difficulty Concentrating: 30 min
    1.2 ± 1
    1.2 ± 1
        Difficulty Concentrating: 1 hour
    1.1 ± 1
    1.2 ± 1.1
        Difficulty Concentrating: 2 hour
    1.3 ± 1.1
    1.2 ± 1.1
    No statistical analyses for this end point

    Secondary: Percentage of Subjects in Preference of Treatment With Respect to Craving Relief

    		 Close Top of page
    End point title
    		 Percentage of Subjects in Preference of Treatment With Respect to Craving Relief
    End point description
    Product preference was decided by asking the question at the end of the last treatment visit that which of the two treatments do you prefer with regards to relief of urges to smoke?. Full analysis set population included all randomized subjects with any efficacy assessments.
    End point type
    Secondary
    End point timeframe
    End of visit 2
    End point values
    		 Nicorette ONS (Treatment A) Tabex (Treatment B)
    Number of subjects analysed
    59
    56
    Units: percentage of subjects
        number (not applicable)
    64.8
    35.2
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment Emergent Adverse Events

    		 Close Top of page
    End point title
    		 Number of Subjects With Treatment Emergent Adverse Events
    End point description
    An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between administration of study drug and up to end of visit 2 that were absent before treatment or that worsened relative to pretreatment state. All subjects who received at least one dose of treatment were included in the safety analysis set.
    End point type
    Secondary
    End point timeframe
    End of Visit 2
    End point values
    		 Nicorette ONS (Treatment A) Tabex (Treatment B)
    Number of subjects analysed
    59
    56
    Units: Subjects
    52
    13
    No statistical analyses for this end point

    Secondary: Time to a 50 Percent (%) Reduction From Baseline Intensity of Urges to Smoke Score

    		 Close Top of page
    End point title
    		 Time to a 50 Percent (%) Reduction From Baseline Intensity of Urges to Smoke Score
    End point description
    Kaplan-Meier survival estimates method was used for the time to 50% reduction in urges to smoke. Full analysis set population included all randomized subjects with any efficacy assessments. Here '99999' represents that no estimate was available for median and confidence interval for this specific outcome result.
    End point type
    Secondary
    End point timeframe
    up to 2 hours
    End point values
    		 Nicorette ONS (Treatment A) Tabex (Treatment B)
    Number of subjects analysed
    58
    56
    Units: Minutes
    median (confidence interval 95%)
        25% quartiles
    0.491 (0.39 to 0.794)
    11.69 (5.2 to 19.48)
        50% quartiles
    4.364 (0.806 to 8.361)
    54.01 (19.48 to 99999)
        75% quartiles
    68.19 (8.361 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Time to a 75 Percent (%) Reduction From Baseline Intensity of Urges to Smoke Score

    		 Close Top of page
    End point title
    		 Time to a 75 Percent (%) Reduction From Baseline Intensity of Urges to Smoke Score
    End point description
    Kaplan-Meier survival estimates method was used for the time to 25% reduction in urges to smoke. Full analysis set population included all randomized subjects with any efficacy assessments. Here '99999' represents that no estimate was available for median and confidence interval for this specific outcome result.
    End point type
    Secondary
    End point timeframe
    up to 2 hours
    End point values
    		 Nicorette ONS (Treatment A) Tabex (Treatment B)
    Number of subjects analysed
    58
    56
    Units: Minutes
    median (confidence interval 95%)
        25% quartiles
    0.876 (0.585 to 2.885)
    75.52 (23.12 to 99999)
        50% quartiles
    33.17 (9.868 to 99999)
    99999 (99999 to 99999)
        75% quartiles
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Time to a 90 Percent (%) Reduction From Baseline Intensity of Urges to Smoke Score

    		 Close Top of page
    End point title
    		 Time to a 90 Percent (%) Reduction From Baseline Intensity of Urges to Smoke Score
    End point description
    Kaplan-Meier survival estimates method was used for the time to 90% reduction in urges to smoke. Full analysis set population included all randomized subjects with any efficacy assessments. Here '99999' represents that no estimate was available for median and confidence interval for this specific outcome result.
    End point type
    Secondary
    End point timeframe
    up to 2 hours
    End point values
    		 Nicorette ONS (Treatment A) Tabex (Treatment B)
    Number of subjects analysed
    58
    56
    Units: Minutes
    median (confidence interval 95%)
        25% quartiles
    3.218 (0.785 to 99999)
    99999 (74.53 to 99999)
        50% quartiles
    99999 (99999 to 99999)
    99999 (99999 to 99999)
        75% quartiles
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Attaining 25%, 50%, 75%, and 90% Reduced Craving Score Compared to Baseline

    		 Close Top of page
    End point title
    		 Percentage of Subjects Attaining 25%, 50%, 75%, and 90% Reduced Craving Score Compared to Baseline
    End point description
    Full analysis set population included all randomized subjects with any efficacy assessments.
    End point type
    Secondary
    End point timeframe
    upto 2 hours
    End point values
    		 Nicorette ONS (Treatment A) Tabex (Treatment B)
    Number of subjects analysed
    58
    56
    Units: Percentage of subjects
    number (not applicable)
        25% Reduction (30 sec)
    43.1
    5.4
        25% Reduction (45 sec)
    53.4
    8.9
        25% Reduction (1 min)
    58.6
    10.7
        25% Reduction (3 min)
    72.9
    23.2
        25% Reduction (5 min)
    81.4
    32.1
        25% Reduction (10 min)
    83.1
    39.3
        50% Reduction (30 sec)
    27.6
    1.8
        50% Reduction (45 sec)
    32.8
    1.8
        50% Reduction (1 min)
    41.4
    3.6
        50% Reduction (3 min)
    47.5
    5.4
        50% Reduction (5 min)
    54.2
    12.5
        50% Reduction (10 min)
    64.4
    19.6
        75% Reduction (30 sec)
    6.9
    1.8
        75% Reduction (45 sec)
    24.1
    1.8
        75% Reduction (1 min)
    25.9
    1.8
        75% Reduction (3 min)
    37.3
    3.6
        75% Reduction (5 min)
    37.3
    3.6
        75% Reduction (10 min)
    39
    5.4
        90% Reduction (30 sec)
    0
    1.8
        90% Reduction (45 sec)
    12.1
    1.8
        90% Reduction (1 min)
    15.5
    1.8
        90% Reduction (3 min)
    22
    1.8
        90% Reduction (5 min)
    30.5
    1.8
        90% Reduction (10 min)
    30.5
    3.6
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Attaining 25% Reduced Craving Score Compared to Baseline in Comparisons of ONS vs. Tabex

    		 Close Top of page
    End point title
    		 Percentage of Subjects Attaining 25% Reduced Craving Score Compared to Baseline in Comparisons of ONS vs. Tabex
    End point description
    For the outcome classification in terms of Success or Failure in a given time frame the first outcome was the outcome during treatment with ONS 2 mg whereas the second outcome refers to treatment with Tabex
    End point type
    Secondary
    End point timeframe
    upto 2 hours
    End point values
    		 ONS Versus (vs.) Tabex
    Number of subjects analysed
    54
    Units: Percentage of subjects
    number (not applicable)
        0-30 sec (Fail, Fail)
    29
        0-30 sec (Success, Fail)
    21
        0-30 sec (Success, Success)
    3
        0-45 sec (Fail, Fail)
    24
        0-45 sec (Success, Fail)
    24
        0-45 sec (Success, Success)
    5
        0-1 min (Fail, Fail)
    22
        0-1 min (Success, Fail)
    25
        0-1 min (Success, Success)
    6
        0-3 min (Fail, Fail)
    15
        0-3 min (Success, Fail)
    27
        0-3 min (Success, Success)
    12
        0-5 min (Fail, Fail)
    10
        0-5 min (Fail, Success)
    1
        0-5 min (Success, Fail)
    27
        0-5 min (Success, Success)
    16
        0-10 min (Fail, Fail)
    9
        0-10 min (Fail, Success)
    1
        0-10 min (Success, Fail)
    24
        0-10 min (Success, Success)
    20
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Attaining 50% Reduced Craving Score Compared to Baseline in Comparisons of ONS vs. Tabex

    		 Close Top of page
    End point title
    		 Percentage of Subjects Attaining 50% Reduced Craving Score Compared to Baseline in Comparisons of ONS vs. Tabex
    End point description
    For the outcome classification in terms of Success or Failure in a given time frame the first outcome was the outcome during treatment with ONS 2 mg whereas the second outcome refers to treatment with Tabex. Full analysis set population included all randomized subjects with any efficacy assessments.
    End point type
    Secondary
    End point timeframe
    up to 2 hours
    End point values
    		 ONS Versus (vs.) Tabex
    Number of subjects analysed
    54
    Units: percentage of subjects
    number (not applicable)
        0-30 sec (Fail, Fail)
    38
        0-30 sec (Success, Fail)
    14
        0-30 sec (Success, Success)
    1
        0-45 sec (Fail, Fail)
    35
        0-45 sec (Success, Fail)
    17
        0-45 sec (Success, Success)
    1
        0-1 min (Fail, Fail)
    31
        0-1 min (Success, Fail)
    20
        0-1 min (Success, Success)
    2
        0-3 min (Fail, Fail)
    28
        0-3 min (Success, Fail)
    23
        0-3 min (Success, Success)
    3
        0-5 min (Fail, Fail)
    23
        0-5 min (Fail, Success)
    1
        0-5 min (Success, Fail)
    24
        0-5 min (Success, Success)
    6
        0-10 min (Fail, Fail)
    18
        0-10 min (Fail, Success)
    1
        0-10 min (Success, Fail)
    26
        0-10 min (Success, Success)
    9
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Attaining 75% Reduced Craving Score Compared to Baseline in Comparisons of ONS vs. Tabex

    		 Close Top of page
    End point title
    		 Percentage of Subjects Attaining 75% Reduced Craving Score Compared to Baseline in Comparisons of ONS vs. Tabex
    End point description
    For the outcome classification in terms of Success or Failure in a given time frame the first outcome was the outcome during treatment with ONS 2 mg whereas the second outcome refers to treatment with Tabex. Full analysis set population included all randomized subjects with any efficacy assessments.
    End point type
    Secondary
    End point timeframe
    up to 2 hours
    End point values
    		 ONS Versus (vs.) Tabex
    Number of subjects analysed
    54
    Units: percentage of subjects
    number (not applicable)
        0-30 sec (Fail, Fail)
    48
        0-30 sec (Success, Fail)
    1
        0-30 sec (Success, Success)
    4
        0-45 sec (Fail, Fail)
    40
        0-45 sec (Success, Fail)
    12
        0-45 sec (Success, Success)
    1
        0-1 min (Fail, Fail)
    39
        0-1 min (Success, Fail)
    13
        0-1 min (Success, Success)
    1
        0-3 min (Fail, Fail)
    34
        0-3 min (Success, Fail)
    18
        0-3 min (Success, Success)
    2
        0-5 min (Fail, Fail)
    34
        0-5 min (Success, Fail)
    18
        0-5 min (Success, Success)
    2
        0-10 min (Fail, Fail)
    32
        0-10 min (Fail, Success)
    1
        0-10 min (Success, Fail)
    19
        0-10 min (Success, Success)
    2
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Attaining 90% Reduced Craving Score Compared to Baseline in Comparisons of ONS vs. Tabex

    		 Close Top of page
    End point title
    		 Percentage of Subjects Attaining 90% Reduced Craving Score Compared to Baseline in Comparisons of ONS vs. Tabex
    End point description
    For the outcome classification in terms of Success or Failure in a given time frame the first outcome was the outcome during treatment with ONS 2 mg whereas the second outcome refers to treatment with Tabex.
    End point type
    Secondary
    End point timeframe
    upto 2 hours
    End point values
    		 ONS Versus (vs.) Tabex
    Number of subjects analysed
    54
    Units: Percentage of subjects
    number (not applicable)
        0-30 sec (Fail, Fail)
    52
        0-30 sec (Fail, Success)
    1
        0-45 sec (Fail, Fail)
    46
        0-45 sec (Success, Fail)
    6
        0-45 sec (Success, Success)
    1
        0-1 min (Fail, Fail)
    45
        0-1 min (Success, Fail)
    7
        0-1 min (Success, Success)
    1
        0-3 min (Fail, Fail)
    42
        0-3 min (Success, Fail)
    11
        0-3 min (Success, Success)
    1
        0-5 min (Fail, Fail)
    37
        0-5 min (Success, Fail)
    16
        0-5 min (Success, Success)
    1
        0-10 min (Fail, Fail)
    36
        0-10 min (Fail, Success)
    1
        0-10 min (Success, Fail)
    16
        0-10 min (Success, Success)
    1
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Screening up to end of treatment visit 2
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Nicorette ONS (Treatment A)
    Reporting group description
    		 All randomized subjects with any efficacy assessments and received nicorette peppermint oromucosal spray 2 milligram (mg) as two consecutive sprays of unit dose of 1 mg at two separate visits.

    Reporting group title
    Tabex (Treatment B)
    Reporting group description
    		 All randomized subjects with any efficacy assessments and received tabex tablet 1.5 mg orally with 150 milliliter (mL) of ambient temperature water.

    Serious adverse events
    		 Nicorette ONS (Treatment A) Tabex (Treatment B)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 56 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Nicorette ONS (Treatment A) Tabex (Treatment B)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    52 / 59 (88.14%)
    9 / 56 (16.07%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 59 (3.39%)
    4 / 56 (7.14%)
         occurrences all number
    2
    5
    Eye disorders
    Lacrimation Increased
         subjects affected / exposed
    12 / 59 (20.34%)
    0 / 56 (0.00%)
         occurrences all number
    12
    0
    Gastrointestinal disorders
    Dysphagia
         subjects affected / exposed
    4 / 59 (6.78%)
    0 / 56 (0.00%)
         occurrences all number
    4
    0
    Nausea
         subjects affected / exposed
    13 / 59 (22.03%)
    2 / 56 (3.57%)
         occurrences all number
    14
    2
    Oral Discomfort
         subjects affected / exposed
    10 / 59 (16.95%)
    0 / 56 (0.00%)
         occurrences all number
    10
    0
    Salivary Hypersecretion
         subjects affected / exposed
    11 / 59 (18.64%)
    0 / 56 (0.00%)
         occurrences all number
    11
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    8 / 59 (13.56%)
    0 / 56 (0.00%)
         occurrences all number
    8
    0
    Hiccups
         subjects affected / exposed
    16 / 59 (27.12%)
    0 / 56 (0.00%)
         occurrences all number
    16
    0
    Throat Irritation
         subjects affected / exposed
    19 / 59 (32.20%)
    1 / 56 (1.79%)
         occurrences all number
    19
    1
    Throat Tightness
         subjects affected / exposed
    5 / 59 (8.47%)
    1 / 56 (1.79%)
         occurrences all number
    5
    1
    Skin and subcutaneous tissue disorders
    Hyperhidrosis
         subjects affected / exposed
    3 / 59 (5.08%)
    0 / 56 (0.00%)
         occurrences all number
    3
    0
    Pruritus
         subjects affected / exposed
    0 / 59 (0.00%)
    3 / 56 (5.36%)
         occurrences all number
    0
    3
    Psychiatric disorders
    Hypervigilance
         subjects affected / exposed
    3 / 59 (5.08%)
    1 / 56 (1.79%)
         occurrences all number
    3
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 May 2016
    Amendment included the changes/addition of procedure and texts in following sections; Independent ethics committee, Ethical conduct of the study; Regulatory authority, Risk benefit evaluation, Rationale, Previous and concomitant medications, Determination of sample size, Analysis of primary efficacy endpoints, Study monitoring, Case report forms / Electronic data capture and list of references.

    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
    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-Wed Apr 24 01:31:10 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA