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    Clinical Trial Results:
    A Double-Blind, Placebo Controlled Study of Pharmacodynamic Effects Of 4 Mg Nicotine Gum. A Study in Healthy Smokers Willing to Quit

    Summary
    EudraCT number
    		 2018-004229-10
    Trial protocol
    		 PL  
    Global end of trial date
    26 Sep 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 May 2020
    First version publication date
    28 May 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CCSSMC000766
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    McNeil AB
    Sponsor organisation address
    Norrbroplatsen 2, Helsingborg, Sweden, 25109
    Public contact
    McNeil AB, Global Regulatory Affairs, 0046 42288000,
    Scientific contact
    McNeil AB, Global Regulatory Affairs, 0046 42288000,
    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
    26 Sep 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Sep 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of study was to evaluate the effect of 4 milligrams (mg) nicotine chewing gum on subjects’ perceived relief of overall withdrawal symptoms including urges to smoke, compared to placebo over the first 2 treatment days.
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices (GCP) and applicable regulatory requirements. Safety was evaluated by examining the incidence and type of adverse events, changes in clinical laboratory tests and vital signs.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    20 Aug 2019
    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: 220
    Worldwide total number of subjects
    220
    EEA total number of subjects
    220
    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)
    220
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Overall, 220 subjects were randomized: 110 subjects received placebo and 110 subjects received active treatment.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Subjects received matching placebo Freshfruit E104 gum (maximum 15 gums per day) from Days 1 to 14 or until day before end of study visit.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Medicated chewing-gum
    Routes of administration
    Oromucosal use
    Dosage and administration details
    Subjects received matching placebo Freshfruit E104 gum from Days 1 to 14 or until day before end of study visit.

    Arm title
    		 Nicorette Freshfruit Gum 4 mg
    Arm description
    		 Subjects received Nicorette Freshfruit gum 4 milligrams (mg) maximum 15 gums per day orally from Days 1 to 14 or until day before end of study visit.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nicorette Freshfruit Gum
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Medicated chewing-gum
    Routes of administration
    Oromucosal use
    Dosage and administration details
    Subjects received Nicorette Freshfruit gum 4 mg from Days 1 to 14 or until day before end of study visit.

    Number of subjects in period 1
    		Placebo Nicorette Freshfruit Gum 4 mg
    Started
    110
    110
    Completed
    108
    108
    Not completed
    2
    2
         Consent withdrawn by subject
    -
    2
         Lost to follow-up
    2
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received matching placebo Freshfruit E104 gum (maximum 15 gums per day) from Days 1 to 14 or until day before end of study visit.

    Reporting group title
    Nicorette Freshfruit Gum 4 mg
    Reporting group description
    		 Subjects received Nicorette Freshfruit gum 4 milligrams (mg) maximum 15 gums per day orally from Days 1 to 14 or until day before end of study visit.

    Reporting group values
    		 Placebo Nicorette Freshfruit Gum 4 mg Total
    Number of subjects
    		 110 110 220
    Title for AgeCategorical
    Units: subjects
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 110 110 220
        From 65 to 84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Title for AgeContinuous
    Units: years
        arithmetic mean (standard deviation)
    		 37.4 ± 10.95 36.6 ± 11.54 -
    Title for Gender
    Units: subjects
        Female
    		 60 66 126
        Male
    		 50 44 94

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received matching placebo Freshfruit E104 gum (maximum 15 gums per day) from Days 1 to 14 or until day before end of study visit.

    Reporting group title
    Nicorette Freshfruit Gum 4 mg
    Reporting group description
    		 Subjects received Nicorette Freshfruit gum 4 milligrams (mg) maximum 15 gums per day orally from Days 1 to 14 or until day before end of study visit.

    Primary: Mean of Daily Self-assessed Visual Analog Scale (VAS) Ratings of Relief of Overall Withdrawal Symptoms Over Days 1 and 2

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    End point title
    		 Mean of Daily Self-assessed Visual Analog Scale (VAS) Ratings of Relief of Overall Withdrawal Symptoms Over Days 1 and 2
    End point description
    VAS is self-assessed tool to record the treatment effects on overall relief of withdrawal symptoms. VAS scale ranges from 0 to 100 millimetre (mm). 0 indicated no relief of withdrawal symptoms and 100 indicated complete relief of withdrawal symptoms. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Days 1 and 2
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    110
    109
    Units: unit on scale
        least squares mean (standard error)
    26.64 ± 1.971
    32.53 ± 1.980
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    219
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.036
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    5.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.38
         upper limit
    		 11.39

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Overall Withdrawal Symptoms Over Days 3 to 7

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Overall Withdrawal Symptoms Over Days 3 to 7
    End point description
    VAS is self-assessed tool to record the treatment effects on overall relief of withdrawal symptoms. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of withdrawal symptoms and 100 indicated complete relief of withdrawal symptoms. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 3 to 7
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    107
    110
    Units: unit on scale
        least squares mean (standard error)
    33.08 ± 2.107
    38.91 ± 2.078
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    217
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.05
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    5.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 11.66

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Overall Withdrawal Symptoms Over Days 8 to 14

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Overall Withdrawal Symptoms Over Days 8 to 14
    End point description
    VAS is self-assessed tool to record the treatment effects on overall relief of withdrawal symptoms. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of withdrawal symptoms and 100 indicated complete relief of withdrawal symptoms. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 8 to 14.
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    108
    106
    Units: unit on scale
        least squares mean (standard error)
    37.38 ± 2.483
    46.71 ± 2.506
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    214
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.009
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    9.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.37
         upper limit
    		 16.28

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Urge to Smoke Over Days 1 and 2

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Urge to Smoke Over Days 1 and 2
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of urge to smoke. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of urge to smoke and 100 indicated complete relief of urge to smoke. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 1 and 2
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    110
    108
    Units: unit on scale
        least squares mean (standard error)
    25.93 ± 1.965
    33.06 ± 1.983
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    218
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.011
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    7.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.63
         upper limit
    		 12.6

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Urge to Smoke Over Days 3 to 7

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Urge to Smoke Over Days 3 to 7
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of urge to smoke. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of urge to smoke and 100 indicated complete relief of urge to smoke. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 3 to 7
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    103
    108
    Units: unit on scale
        least squares mean (standard error)
    31.88 ± 2.097
    39.73 ± 2.048
    Statistical analysis title
    		 statistical analysis 1
    Statistical analysis description
    Database auto-calculates total number of subjects erroneously, analyzed number of subjects were 103.
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    211
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.008
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    7.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.07
         upper limit
    		 13.6

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Urge to Smoke Over Days 8 to 14

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Urge to Smoke Over Days 8 to 14
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of urge to smoke. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of urge to smoke and 100 indicated complete relief of urge to smoke. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 8 to 14
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    96
    92
    Units: unit on scale
        least squares mean (standard error)
    35.79 ± 2.511
    43.13 ± 2.565
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.042
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    7.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.26
         upper limit
    		 14.43

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of depressed mood Over Days 1 and 2

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of depressed mood Over Days 1 and 2
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of depressed mood. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of depressed mood and 100 indicated complete relief of depressed mood. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 1 and 2
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    31
    33
    Units: unit on scale
        least squares mean (standard error)
    23.90 ± 3.286
    19.24 ± 3.185
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    64
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.312
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    -4.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.81
         upper limit
    		 4.49

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of depressed mood Over Days 3 to 7

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of depressed mood Over Days 3 to 7
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of depressed mood. VAS scale ranges from Zero to 100 mm. Zero indicated no relief of depressed mood and 100 indicated complete relief of depressed mood. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 3 to 7
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    6
    10
    Units: unit on scale
        least squares mean (standard error)
    21.86 ± 7.288
    30.97 ± 5.646
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    16
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.34
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    9.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.66
         upper limit
    		 28.89

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of depressed mood Over Days 8 to 14

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of depressed mood Over Days 8 to 14
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of depressed mood. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of depressed mood and 100 indicated complete relief of depressed mood. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 8 to 14
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    3
    6
    Units: unit on scale
        least squares mean (standard error)
    29.85 ± 13.165
    37.83 ± 9.309
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    9
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.636
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    7.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30.15
         upper limit
    		 46.11

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of irritability Over Days 1 and 2

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of irritability Over Days 1 and 2
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of irritability. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of irritability and 100 indicated complete relief of irritability. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 1 and 2
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    48
    59
    Units: unit on scale
        least squares mean (standard error)
    24.79 ± 3.026
    27.01 ± 2.730
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.588
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    0.588
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.86
         upper limit
    		 10.3

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of irritability Over Days 3 to 7

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of irritability Over Days 3 to 7
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of irritability. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of irritability and 100 indicated complete relief of irritability. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 3 to 7
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    16
    21
    Units: unit on scale
        least squares mean (standard error)
    28.90 ± 5.058
    32.88 ± 4.415
    Statistical analysis title
    		 Statistical analysis
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.558
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    3.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.66
         upper limit
    		 17.61

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of irritability Over Days 8 to 14

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of irritability Over Days 8 to 14
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of irritability. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of irritability and 100 indicated complete relief of irritability. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 8 to 14
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    8
    11
    Units: unit on scale
        least squares mean (standard error)
    51.56 ± 6.678
    40.66 ± 5.695
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.231
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    -10.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -29.42
         upper limit
    		 7.62

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Frustration Over Days 1 and 2

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Frustration Over Days 1 and 2
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of frustration. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of frustration and 100 indicated complete relief of frustration. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 1 and 2
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    31
    47
    Units: unit on scale
        least squares mean (standard error)
    19.79 ± 3.761
    26.48 ± 3.054
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.171
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    6.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.96
         upper limit
    		 16.34

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Frustration Over Days 3 to 7

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Frustration Over Days 3 to 7
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of frustration. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of frustration and 100 indicated complete relief of frustration. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 3 to 7
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    8
    12
    Units: unit on scale
        least squares mean (standard error)
    27.13 ± 7.033
    37.52 ± 5.742
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.268
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    0.268
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.69
         upper limit
    		 29.46

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Frustration Over Days 8 to 14

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Frustration Over Days 8 to 14
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of frustration. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of frustration and 100 indicated complete relief of frustration. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 8 to 14
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    5
    8
    Units: unit on scale
        least squares mean (standard error)
    35.79 ± 9.552
    46.07 ± 7.551
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    13
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.416
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    0.416
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.52
         upper limit
    		 37.08

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Restlessness Over Days 1 to 2

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Restlessness Over Days 1 to 2
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of restlessness. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of restlessness and 100 indicated complete relief of restlessness. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 1 and 2
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    53
    56
    Units: unit on scale
        least squares mean (standard error)
    23.25 ± 2.807
    26.22 ± 2.731
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.45
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    2.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.8
         upper limit
    		 10.73

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Restlessness Over Days 3 to 7

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Restlessness Over Days 3 to 7
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of restlessness. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of restlessness and 100 indicated complete relief of restlessness. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 3 to 7
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    22
    27
    Units: unit on scale
        least squares mean (standard error)
    35.05 ± 4.426
    35.12 ± 3.995
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.992
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.93
         upper limit
    		 12.06

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Restlessness Over Days 8 to 14

    		 Close Top of page
    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Restlessness Over Days 8 to 14
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of restlessness. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of restlessness and 100 indicated complete relief of restlessness. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 8 to 14
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    15
    18
    Units: unit on scale
        least squares mean (standard error)
    49.53 ± 5.312
    40.65 ± 4.849
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    33
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.226
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    0.226
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.55
         upper limit
    		 5.79

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Increased Appetite Over Days 1 to 2

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Increased Appetite Over Days 1 to 2
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of increased appetite. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of increased appetite and 100 indicated complete relief of increased appetite. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 1 and 2
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    35
    46
    Units: unit on scale
        least squares mean (standard error)
    20.13 ± 3.557
    27.22 ± 3.103
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.137
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    7.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.31
         upper limit
    		 16.48

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief Increased Appetite Over Days 3 to 7

    		 Close Top of page
    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief Increased Appetite Over Days 3 to 7
    End point description
    VAS is self-assessed tool to record the treatment effects on relief increased appetite. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of increased appetite and 100 indicated complete relief of increased appetite. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 3 to 7
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    15
    15
    Units: unit on scale
        least squares mean (standard error)
    35.06 ± 5.784
    35.86 ± 5.784
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.923
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.96
         upper limit
    		 17.56

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief Increased Appetite Over Days 8 to 14

    		 Close Top of page
    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief Increased Appetite Over Days 8 to 14
    End point description
    VAS is self-assessed tool to record the treatment effects on relief increased appetite. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of increased appetite and 100 indicated complete relief of increased appetite. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 8 to 14
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    7
    11
    Units: unit on scale
        least squares mean (standard error)
    41.02 ± 8.215
    40.02 ± 6.553
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.926
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    -0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.27
         upper limit
    		 21.28

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Stress Over Days 1 to 2

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Stress Over Days 1 to 2
    End point description
    VAS is self-assessed tool to record the treatment effects of relief of stress. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of stress and 100 indicated complete relief of stress. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 1 and 2
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    49
    50
    Units: unit on scale
        least squares mean (standard error)
    23.17 ± 2.656
    20.48 ± 2.630
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    99
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.473
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    -2.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.11
         upper limit
    		 4.72

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Stress Over Days 3 to 7

    		 Close Top of page
    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Stress Over Days 3 to 7
    End point description
    VAS is self-assessed tool to record the treatment effects of relief of stress. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of stress and 100 indicated complete relief of stress. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 3 to 7
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    10
    22
    Units: unit on scale
        least squares mean (standard error)
    38.47 ± 6.625
    31.83 ± 4.467
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.413
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    -6.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.95
         upper limit
    		 9.69

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Stress Over Days 8 to 14

    		 Close Top of page
    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Stress Over Days 8 to 14
    End point description
    VAS is self-assessed tool to record the treatment effects of relief of stress. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of stress and 100 indicated complete relief of stress. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 8 to 14
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    8
    11
    Units: unit on scale
        least squares mean (standard error)
    38.99 ± 9.275
    45.87 ± 7.910
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.58
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    6.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.84
         upper limit
    		 32.6

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Difficulty Concentrating Over Days 1 to 2

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    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Difficulty Concentrating Over Days 1 to 2
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of difficulty concentrating. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of difficulty concentrating and 100 indicated complete relief of difficulty concentrating. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 1 and 2
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    26
    33
    Units: unit on scale
        least squares mean (standard error)
    23.25 ± 3.509
    22.74 ± 3.114
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    59
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.914
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    -0.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.9
         upper limit
    		 8.89

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Difficulty Concentrating Over Days 3 to 7

    		 Close Top of page
    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Difficulty Concentrating Over Days 3 to 7
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of difficulty concentrating. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of difficulty concentrating and 100 indicated complete relief of difficulty concentrating. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 3 to 7
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    4
    10
    Units: unit on scale
        least squares mean (standard error)
    31.95 ± 9.275
    33.87 ± 5.866
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    14
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.864
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    1.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22
         upper limit
    		 25.83

    Secondary: Mean of Daily Self-assessed VAS Ratings of Relief of Difficulty Concentrating Over Days 8 to 14

    		 Close Top of page
    End point title
    		 Mean of Daily Self-assessed VAS Ratings of Relief of Difficulty Concentrating Over Days 8 to 14
    End point description
    VAS is self-assessed tool to record the treatment effects on relief of difficulty concentrating. VAS scale ranges from 0 to 100 mm. 0 indicated no relief of difficulty concentrating and 100 indicated complete relief of difficulty concentrating. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Days 8 to 14
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    4
    5
    Units: unit on scale
        least squares mean (standard error)
    49.76 ± 9.333
    41.86 ± 8.348
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    9
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.548
    Method
    		 ANOVA
    Parameter type
    		 Estimated mean difference
    Point estimate
    -7.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -37.51
         upper limit
    		 21.71

    Secondary: Perceived Change in Self-efficacy in Quitting Smoking at Week 1 Visit

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    End point title
    		 Perceived Change in Self-efficacy in Quitting Smoking at Week 1 Visit
    End point description
    Subjects' perceived change in self-efficacy in quitting smoking was recorded. Self-efficacy in quitting smoking was recorded on a 7-grade scale, where 1 indicated much less confident; 7 indicated much more confident. Missing data were imputed with ‘Less confident (2)’ on a 7-grade scale. Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Week 1
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    110
    110
    Units: unit on scale
        arithmetic mean (standard deviation)
    4.7 ± 1.15
    5.0 ± 1.20
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    220
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.051
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Self- assessed Ratings of Change in Willpower to Quit Smoking After 2 Days

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    End point title
    		 Self- assessed Ratings of Change in Willpower to Quit Smoking After 2 Days
    End point description
    Subjects’ self- assessed ratings of change in willpower to quit smoking was recorded. Self- assessed ratings in quitting smoking was recorded on a 7-grade scale, where 1 indicated much weaker willpower; 7 indicated much stronger willpower. Missing data were imputed with ‘Weaker (2)’ on 7-grade categorical scale for subjects who discontinued study prematurely or imputed using last observation carried forward for subjects who completed the study. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 2
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    110
    107
    Units: unit on scale
        arithmetic mean (standard deviation)
    4.4 ± 1.14
    4.5 ± 1.14
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    217
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.452
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Self- assessed Ratings of Change in Willpower to Quit Smoking After 7 Days

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    End point title
    		 Self- assessed Ratings of Change in Willpower to Quit Smoking After 7 Days
    End point description
    Subjects’ self- assessed ratings of change in willpower to quit smoking was recorded. Self- assessed ratings in quitting smoking was recorded on a 7-grade scale, where 1 indicated much weaker willpower; 7 indicated much stronger willpower. Missing data were imputed with ‘Weaker (2)’ on 7-grade categorical scale for subjects who discontinued study prematurely or imputed using last observation carried forward for subjects who completed the study. Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Day 7
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    110
    110
    Units: unit on scale
        arithmetic mean (standard deviation)
    4.8 ± 1.11
    5.1 ± 1.05
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    220
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.05
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Self- assessed Ratings of Change in Willpower to Quit Smoking After 14 Days

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    End point title
    		 Self- assessed Ratings of Change in Willpower to Quit Smoking After 14 Days
    End point description
    Subjects’ self- assessed ratings of change in willpower to quit smoking was recorded. Self- assessed ratings in quitting smoking was recorded on a 7-grade scale, where 1 indicated much weaker willpower; 7 indicated much stronger willpower. Missing data were imputed with ‘Weaker (2)’ on 7-grade categorical scale for subjects who discontinued study prematurely or imputed using last observation carried forward for subjects who completed the study. Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Day 14
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    110
    110
    Units: unit on scale
        arithmetic mean (standard deviation)
    4.8 ± 1.32
    5.3 ± 1.29
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Placebo v Nicorette Freshfruit Gum 4 mg
    Number of subjects included in analysis
    220
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.008
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Self- assessed Ratings of Change in Willpower to Resist a Cigarette After 2 Days

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    End point title
    		 Self- assessed Ratings of Change in Willpower to Resist a Cigarette After 2 Days
    End point description
    Subjects’ self- assessed ratings of change in willpower to resist a cigarette was recorded. Self- assessed ratings in quitting smoking was recorded on a 7-grade scale, where 1 indicated much weaker willpower; 7 indicated much stronger willpower. Missing data were imputed with ‘Weaker (2)’ on 7-grade categorical scale for subjects who discontinued study prematurely or imputed using last observation carried forward for subjects who completed the study. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'N' signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 2
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    110
    107
    Units: unit on scale
        arithmetic mean (standard deviation)
    4.4 ± 1.18
    4.6 ± 1.24
    Statistical analysis title
    		 statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    217
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.213
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Self- assessed Ratings of Change in Willpower to Resist a Cigarette After 7 Days

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    End point title
    		 Self- assessed Ratings of Change in Willpower to Resist a Cigarette After 7 Days
    End point description
    Subjects’ self- assessed ratings of change in willpower to resist a cigarette was recorded. Self- assessed ratings in quitting smoking was recorded on a 7-grade scale, where 1 indicated much weaker willpower; 7 indicated much stronger willpower. Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Day 7
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    110
    110
    Units: unit on scale
        arithmetic mean (standard deviation)
    4.7 ± 1.11
    5.0 ± 1.21
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    220
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.045
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Self- assessed Ratings of Change in Willpower to Resist a Cigarette After 14 Days

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    End point title
    		 Self- assessed Ratings of Change in Willpower to Resist a Cigarette After 14 Days
    End point description
    Subjects’ self- assessed ratings of change in willpower to resist a cigarette was recorded. Self- assessed ratings in quitting smoking was recorded on a 7-grade scale, where 1 indicated much weaker willpower; 7 indicated much stronger willpower. Missing data were imputed with ‘Weaker (2)’ on 7-grade categorical scale for subjects who discontinued study prematurely or imputed using last observation carried forward for subjects who completed the study. Full analysis set included all randomized subjects who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Day 14
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    110
    110
    Units: unit on scale
        arithmetic mean (standard deviation)
    4.7 ± 1.29
    5.2 ± 1.25
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    220
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Number of Subjects with Self-reported and CO-verified Smoking Abstinence at Week 1 and at the End of Study

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    End point title
    		 Number of Subjects with Self-reported and CO-verified Smoking Abstinence at Week 1 and at the End of Study
    End point description
    Number of subjects with self-reported and CO-verified smoking abstinence at Week 1 and at the end of study visits was reported. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'n' signifies number of subjects analyzed for specific arm.
    End point type
    Secondary
    End point timeframe
    Week 1 and Week 2 (end of study)
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    110
    110
    Units: Subjects
        Week 1 (n=109, 108)
    1
    1
        End of study (n=108, 108)
    3
    2
    Statistical analysis title
    		 Statistical analysis week 1
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    220
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.369
    Method
    		 ANOVA
    Parameter type
    		 Estimated Rate mean difference
    Point estimate
    -1.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.44
         upper limit
    		 1.72
    Statistical analysis title
    		 Statistical analysis (end of study)
    Comparison groups
    Nicorette Freshfruit Gum 4 mg v Placebo
    Number of subjects included in analysis
    220
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.999
    Method
    		 ANOVA
    Parameter type
    		 Estimated Rate mean difference
    Point estimate
    -0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.04
         upper limit
    		 2.19

    Secondary: Mean Daily Number of Gums Used by study Subjects on Days 1 to 14

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    End point title
    		 Mean Daily Number of Gums Used by study Subjects on Days 1 to 14
    End point description
    Mean daily number of gums used by study subjects on Days 1 to 14 were reported. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'n' signifies number of subjects analyzed for specific arm.
    End point type
    Secondary
    End point timeframe
    Days 1 to 14
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    110
    110
    Units: number of gums
    arithmetic mean (standard error)
        Day 1 (n=110, 109)
    8.5 ± 3.50
    7.2 ± 3.10
        Day 2 (n=110, 107)
    9.3 ± 3.43
    8.3 ± 3.61
        Day 3 (n=109, 108)
    9.1 ± 3.16
    8.6 ± 3.61
        Day 4 (n=108, 106)
    9.3 ± 3.63
    8.6 ± 3.62
        Day 5 (n=110, 105)
    9.3 ± 3.74
    8.2 ± 3.74
        Day 6 (n=109, 109)
    9.3 ± 3.68
    8.7 ± 3.76
        Day 7 (n=109, 109)
    9.0 ± 3.67
    8.5 ± 3.41
        Day 8 (n=104, 107)
    9.9 ± 3.69
    8.9 ± 3.70
        Day 9 (n=105, 105)
    9.7 ± 3.55
    9.1 ± 3.74
        Day 10 (n=107, 106)
    9.7 ± 3.65
    8.8 ± 3.78
        Day 11 (n=106, 106)
    9.4 ± 3.98
    8.7 ± 3.84
        Day 12 (n=107, 106)
    9.7 ± 3.70
    8.3 ± 3.84
        Day 13 (n=108, 108)
    10.0 ± 3.59
    8.5 ± 3.67
        Day 14 (n=108, 107)
    9.5 ± 3.92
    8.5 ± 3.78
    No statistical analyses for this end point

    Secondary: Mean Daily Number of Cigarettes Smoked by Study Subjects on Days 1 to 14

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    End point title
    		 Mean Daily Number of Cigarettes Smoked by Study Subjects on Days 1 to 14
    End point description
    Mean daily number of cigarettes smoked by study subjects on Days 1 to 14 were reported. Full analysis set included all randomized subjects who received at least 1 dose of study drug. Here 'n' signifies number of subjects analyzed for specific arm.
    End point type
    Secondary
    End point timeframe
    Days 1 to 14
    End point values
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Number of subjects analysed
    110
    110
    Units: number of cigarettes
    arithmetic mean (standard error)
        Day 1 (n=110, 109)
    14.7 ± 7.22
    13.0 ± 8.45
        Day 2 (n=110, 107)
    13.7 ± 7.79
    11.2 ± 7.93
        Day 3 (n=109, 108)
    12.9 ± 7.46
    10.5 ± 7.21
        Day 4 (n=108, 106)
    12.3 ± 7.90
    10.1 ± 7.56
        Day 5 (n=110, 105)
    11.8 ± 7.11
    10.2 ± 7.59
        Day 6 (n=109, 109)
    11.3 ± 7.39
    9.7 ± 7.39
        Day 7 (n=109, 109)
    11.4 ± 7.62
    8.7 ± 6.57
        Day 8 (n=104, 107)
    11.2 ± 7.79
    9.1 ± 7.25
        Day 9 (n=105, 105)
    10.8 ± 7.44
    8.5 ± 7.07
        Day 10 (n=107, 106)
    10.6 ± 7.25
    8.0 ± 7.37
        Day 11 (n=106, 106)
    10.7 ± 8.12
    7.9 ± 6.98
        Day 12 (n=107, 106)
    10.3 ± 7.63
    8.2 ± 7.02
        Day 13 (n=108, 108)
    10.4 ± 7.50
    7.9 ± 7.33
        Day 14 (n=108, 107)
    10.4 ± 7.83
    7.8 ± 7.17
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 5 weeks
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received matching placebo Freshfruit E104 gum maximum 15 gums per day from Days 1 to 14 or until day before end of study visit.

    Reporting group title
    Nicorette Freshfruit Gum 4 mg
    Reporting group description
    		 Subjects received Nicorette Freshfruit gum 4 milligram (mg) maximum 15 gums per day orally from Days 1 to 14 or until day before end of study visit.

    Serious adverse events
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 110 (0.00%)
    0 / 110 (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
    		 Placebo Nicorette Freshfruit Gum 4 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    10 / 110 (9.09%)
    42 / 110 (38.18%)
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    2 / 110 (1.82%)
    9 / 110 (8.18%)
         occurrences all number
    2
    9
    Headache
         subjects affected / exposed
    4 / 110 (3.64%)
    6 / 110 (5.45%)
         occurrences all number
    5
    6
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    0 / 110 (0.00%)
    18 / 110 (16.36%)
         occurrences all number
    0
    18
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal Pain
         subjects affected / exposed
    0 / 110 (0.00%)
    6 / 110 (5.45%)
         occurrences all number
    0
    6
    Throat Irritation
         subjects affected / exposed
    5 / 110 (4.55%)
    16 / 110 (14.55%)
         occurrences all number
    5
    16

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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