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    Clinical Trial Results:
    Randomised, double-blind, placebo-controlled, complete 3-way cross-over phase IIa trial to investigate safety and efficacy of two THN102 doses in subjects with excessive daytime sleepiness associated with Parkinson’s disease

    Summary
    EudraCT number
    2017-004475-31
    Trial protocol
    HU   CZ  
    Global end of trial date
    20 Dec 2019

    Results information
    Results version number
    v1(current)
    This version publication date
    07 Jul 2021
    First version publication date
    07 Jul 2021
    Other versions
    Summary report(s)
    THN102-202 clinical study report synopsis

    Trial information

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    Trial identification
    Sponsor protocol code
    THN102-202
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03624920
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Theranexus
    Sponsor organisation address
    86 route de Paris, Orsay, France, 91400
    Public contact
    Damien Bouvier, Theranexus S.A., 0033 146548524, damien.bouvier@theranexus.com
    Scientific contact
    Damien Bouvier, Theranexus S.A., 0033 146548524, damien.bouvier@theranexus.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
    18 Dec 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    18 Dec 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Dec 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the safety profile of THN102 (modafinil/flecainide combination) at two doses (200 mg/18 mg and 200 mg/2 mg) versus placebo in subjects with excessive daytime sleepiness associated with Parkinson’s disease (PD).
    Protection of trial subjects
    All subjects were closely monitored during the trial. Subjects who discontinued trial participation prematurely were asked to come to the site for an early discontinuation and follow-up visits to exclude the possibility of an adverse event (AE) being the cause and otherwise to assess if the AE had any potential relationship to the trial medication. Serious adverse events (SAEs) were to be followed-up until resolution or until no further improvement could be expected, and follow-up information was to be recorded by the investigators. SAEs detected after the last subject’s visit, were to be collected if in the investigator’s opinion, they were related either to the investigational medicinal product (IMP) or to the trial procedure. Subjects with electrocardiogram (ECG) signs of left ventricular hypertrophy had to be withdrawn from further participation in the trial and were to be referred to a cardiologist for further examination. Subjects who answered “yes” to point 4 and/or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS), were to be withdrawn from the trial and sent for psychiatric consultation. Subjects with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 5 times the upper limit of normal (ULN), or ALT and AST ≥ 3 times the ULN together with bilirubin ≥ 2 times the ULN were to be withdrawn from the trial.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    12 Jul 2018
    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
    United States: 5
    Country: Number of subjects enrolled
    France: 16
    Country: Number of subjects enrolled
    Germany: 19
    Country: Number of subjects enrolled
    Hungary: 12
    Country: Number of subjects enrolled
    Czechia: 25
    Worldwide total number of subjects
    77
    EEA total number of subjects
    72
    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)
    36
    From 65 to 84 years
    41
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    105 patients were screened and 77 were randomized and 75 were exposed to study medication

    Pre-assignment
    Screening details
    Randomised, double-blind, placebo-controlled, complete 3-way cross-over trial in subjects aged 18 to 80 years with excessive daytime sleepiness associated with Parkinson’s disease. The study consisted of a screening period, followed by three 2-week treatment periods separated by washout periods of 1 to 2 weeks each, and 1-week follow-up.

    Pre-assignment period milestones
    Number of subjects started
    77
    Number of subjects completed
    75 [1]

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    Consent withdrawn by subject: 1
    Reason: Number of subjects
    Protocol deviation: 1
    Notes
    [1] - The number of subjects reported to be in the pre-assignment period is not consistent with the number starting period 1. It is expected that the number completing the pre-assignment period are also present in the arms in period 1.
    Justification: Crossover design
    Period 1
    Period 1 title
    overall trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    Modafinil 100 mg capsules and modafinil placebo capsules as well as flecainide 1 mg or 9 mg capsules and matching placebo capsules were identical in size and appearance, as well as colour of modafinil and respective placebo (orange), and flecainide and respective placebo (white). The packaging and labelling did not allow for any distinction between them.

    Arms
    Are arms mutually exclusive
    No

    Arm title
    THN102 Placebo
    Arm description
    Dosage A
    Arm type
    Placebo

    Investigational medicinal product name
    THN102 placebo
    Investigational medicinal product code
    dose A
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    In this trial, all subjects received the same doses of IMP (modafinil/flecainide 200 mg/2 mg, 200 mg/18 mg and matching placebo). IMP (2 capsules modafinil or placebo plus 2 capsules flecainide or placebo; 4 capsules in total) were to be administered in the morning. The IMP was to be swallowed before meal with 150 mL tap water at 8:00 h (± 1 h). The interval of 24 h between the 2 intakes should be followed. Subjects aged above 65 years were asked to take half a dose of IMP (2 capsules) during the first 3 days of each treatment period, followed by the full IMP dose since the fourth treatment day.

    Arm title
    THN102 200/2
    Arm description
    Dosage B
    Arm type
    Experimental

    Investigational medicinal product name
    THN102 200/2
    Investigational medicinal product code
    Dosage B
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    In this trial, all subjects received the same doses of IMP (modafinil/flecainide 200 mg/2 mg, 200 mg/18 mg and matching placebo). IMP (2 capsules modafinil or placebo plus 2 capsules flecainide or placebo; 4 capsules in total) were to be administered in the morning. The IMP was to be swallowed before meal with 150 mL tap water at 8:00 h (± 1 h). The interval of 24 h between the 2 intakes should be followed. Subjects aged above 65 years were asked to take half a dose of IMP (2 capsules) during the first 3 days of each treatment period, followed by the full IMP dose since the fourth treatment day.

    Arm title
    THN102 200/18
    Arm description
    Dosage C
    Arm type
    Experimental

    Investigational medicinal product name
    THN102 200/18
    Investigational medicinal product code
    dosage C
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    In this trial, all subjects received the same doses of IMP (modafinil/flecainide 200 mg/2 mg, 200 mg/18 mg and matching placebo). IMP (2 capsules modafinil or placebo plus 2 capsules flecainide or placebo; 4 capsules in total) were to be administered in the morning. The IMP was to be swallowed before meal with 150 mL tap water at 8:00 h (± 1 h). The interval of 24 h between the 2 intakes should be followed. Subjects aged above 65 years were asked to take half a dose of IMP (2 capsules) during the first 3 days of each treatment period, followed by the full IMP dose since the fourth treatment day.

    Number of subjects in period 1
    THN102 Placebo THN102 200/2 THN102 200/18
    Started
    68
    72
    73
    Completed
    68
    68
    68
    Not completed
    0
    4
    5
         Protocol deviation
    -
    1
    2
         Adverse event, non-fatal
    -
    3
    3

    Baseline characteristics

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    Baseline characteristics reporting groups [1]
    Reporting group title
    overall trial
    Reporting group description
    -

    Notes
    [1] - The number of subjects reported to be in the baseline period is not equal to the worldwide number of subjects enrolled in the trial. It is expected that these numbers will be the same.
    Justification: among the 77 patients randomized 2 left the study before any IMP intake. These 2 patients have been exluded from the safety set.
    Reporting group values
    overall trial Total
    Number of subjects
    75 75
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    35 35
        From 65-84 years
    40 40
        85 years and over
    0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    63.5 ± 9.35 -
    Gender categorical
    Units: Subjects
        Female
    25 25
        Male
    50 50
    Subject analysis sets

    Subject analysis set title
    Full analysis set
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The Full Analysis Set (FAS) includes all randomised subjects with an evaluable ESS score at the end of at least one treatment period. Evaluability of treatment periods is described in Section 5.6. The efficacy analyses will be conducted on the FAS.

    Subject analysis set title
    SAFETY SET
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    The Safety Set (SS) includes all subjects with at least one IMP administration.

    Subject analysis sets values
    Full analysis set SAFETY SET
    Number of subjects
    72
    75
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    34
    35
        From 65-84 years
    38
    40
        85 years and over
    0
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    63.3 ± 9.43
    63.5 ± 9.35
    Gender categorical
    Units: Subjects
        Female
    24
    25
        Male
    48
    50

    End points

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    End points reporting groups
    Reporting group title
    THN102 Placebo
    Reporting group description
    Dosage A

    Reporting group title
    THN102 200/2
    Reporting group description
    Dosage B

    Reporting group title
    THN102 200/18
    Reporting group description
    Dosage C

    Subject analysis set title
    Full analysis set
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The Full Analysis Set (FAS) includes all randomised subjects with an evaluable ESS score at the end of at least one treatment period. Evaluability of treatment periods is described in Section 5.6. The efficacy analyses will be conducted on the FAS.

    Subject analysis set title
    SAFETY SET
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    The Safety Set (SS) includes all subjects with at least one IMP administration.

    Primary: Epworth Sleeping Scale (ESS)

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    End point title
    Epworth Sleeping Scale (ESS)
    End point description
    Range of the scale : 0 to 24. A low score indicates a good outcome. Results shown are corresponding to a change from baseline of the ESS score.
    End point type
    Primary
    End point timeframe
    2 weeks
    End point values
    THN102 Placebo THN102 200/2 THN102 200/18
    Number of subjects analysed
    68
    69
    71
    Units: ESS score
        least squares mean (standard error)
    -2.4 ± 3.65
    -3.9 ± 4.87
    -3.1 ± 4.12
    Statistical analysis title
    THN102 200/2 vs THN102 placebo A ESS Score
    Statistical analysis description
    Continuous efficacy endpoints – the change from baseline at each key visit (end of treatment period I, II, and III) in ESS, PVT and MoCA - were analysed using a mixed linear regression model, which included the treatment, period, treatment by period interaction, sequence, and baseline scores as fixed effects, and the subject nested within sequence as a random effect.
    Comparison groups
    THN102 200/2 v THN102 Placebo
    Number of subjects included in analysis
    137
    Analysis specification
    Pre-specified
    Analysis type
    superiority [1]
    P-value
    = 0.012 [2]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.3994
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.4861
         upper limit
    -0.3128
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.5492
    Notes
    [1] - Analysis of Epworth Sleepiness Scale Score
    [2] - Estimates are based on the mixed linear regression model with the fixed effects of treatment, period, treatment by period interaction, sequence, baseline score, and the random effect of subjects within sequences.
    Statistical analysis title
    THN102 200/18 vs THN102 placebo A ESS score
    Statistical analysis description
    Continuous efficacy endpoints – the change from baseline at each key visit (end of treatment period I, II, and III) in ESS, PVT and MoCA - were analysed using a mixed linear regression model, which included the treatment, period, treatment by period interaction, sequence, and baseline scores as fixed effects, and the subject nested within sequence as a random effect.
    Comparison groups
    THN102 200/18 v THN102 Placebo
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    superiority [3]
    P-value
    = 0.1769 [4]
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.7427
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.8249
         upper limit
    0.3394
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.547
    Notes
    [3] - Analysis of Epworth Sleepiness Scale Score
    [4] - Estimates are based on the mixed linear regression model with the fixed effects of treatment, period, treatment by period interaction, sequence, baseline score, and the random effect of subjects within sequences.
    Statistical analysis title
    THN102 200/18 vs THN102 200/2 A ESS score
    Statistical analysis description
    Continuous efficacy endpoints – the change from baseline at each key visit (end of treatment period I, II, and III) in ESS, PVT and MoCA - were analysed using a mixed linear regression model, which included the treatment, period, treatment by period interaction, sequence, and baseline scores as fixed effects, and the subject nested within sequence as a random effect.
    Comparison groups
    THN102 200/18 v THN102 Placebo
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    superiority [5]
    P-value
    = 0.2303 [6]
    Method
    mixed linear regression model
    Parameter type
    Mean difference (final values)
    Point estimate
    0.6567
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.4212
         upper limit
    1.7346
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.5449
    Notes
    [5] - Analysis of Epworth Sleepiness Scale Score
    [6] - Estimates are based on the mixed linear regression model with the fixed effects of treatment, period, treatment by period interaction, sequence, baseline score, and the random effect of subjects within sequences.

    Secondary: Psychomotor Vigilance Test (PVT) : Reaction Time (Miliseconds) Change From Baseline

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    End point title
    Psychomotor Vigilance Test (PVT) : Reaction Time (Miliseconds) Change From Baseline
    End point description
    PVT measures reaction time in milliseconds. The results below are corresponding to the reaction time change from baseline Continuous efficacy endpoints – the change from baseline at each key visit (end of treatment period I, II, and III) in ESS, PVT and MoCA - were analysed using a mixed linear regression model, which included the treatment, period, treatment by period interaction, sequence, and baseline scores as fixed effects, and the subject nested within sequence as a random effect.
    End point type
    Secondary
    End point timeframe
    2 weeks
    End point values
    THN102 Placebo THN102 200/2 THN102 200/18
    Number of subjects analysed
    64
    67
    67
    Units: miliseconds
        least squares mean (standard error)
    -16.69 ± 84.983
    -24.92 ± 81.279
    -18.89 ± 78.450
    No statistical analyses for this end point

    Secondary: ESS Responder rate

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    End point title
    ESS Responder rate
    End point description
    ESS score responder rate, defined as the proportion of subjects with at least 25% ESS improvement from baseline, at the end of each treatment period
    End point type
    Secondary
    End point timeframe
    2 weeks
    End point values
    THN102 Placebo THN102 200/2 THN102 200/18
    Number of subjects analysed
    68
    70
    72
    Units: count of participant
        number (not applicable)
    68
    69
    71
    Statistical analysis title
    ESS Responder rate THN102 200/2 vs placebo
    Statistical analysis description
    Categorical efficacy endpoints – absence of residual somnolence and ESS responder status at each key visit – were analysed using a generalised linear mixed regression model (GLMM), with the treatment, period, treatment by period interaction, sequence, and baseline scores as fixed effects, and the subject nested within sequence as a random effect.
    Comparison groups
    THN102 Placebo v THN102 200/2
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1209
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.9766
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.8342
         upper limit
    4.6835
    Statistical analysis title
    ESS Responder rate THN102 200/18 vs placebo
    Statistical analysis description
    Categorical efficacy endpoints – absence of residual somnolence and ESS responder status at each key visit – were analysed using a generalised linear mixed regression model (GLMM), with the treatment, period, treatment by period interaction, sequence, and baseline scores as fixed effects, and the subject nested within sequence as a random effect.
    Comparison groups
    THN102 200/18 v THN102 Placebo
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3534
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.4985
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.6357
         upper limit
    3.5323
    Statistical analysis title
    THN102 200/18 vs 200/2
    Statistical analysis description
    Categorical efficacy endpoints – absence of residual somnolence and ESS responder status at each key visit – were analysed using a generalised linear mixed regression model (GLMM), with the treatment, period, treatment by period interaction, sequence, and baseline scores as fixed effects, and the subject nested within sequence as a random effect.
    Comparison groups
    THN102 200/18 v THN102 200/2
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.4971
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.7581
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.3397
         upper limit
    1.6919

    Secondary: ESS Patients in remission

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    End point title
    ESS Patients in remission
    End point description
    Number of patients in remission (=without residual sleepiness), i.e. ESS < 11 at the end of each treatment period
    End point type
    Secondary
    End point timeframe
    2 weeks
    End point values
    THN102 Placebo THN102 200/2 THN102 200/18
    Number of subjects analysed
    68
    70
    72
    Units: count of participant
        number (not applicable)
    68
    69
    71
    Statistical analysis title
    ESS remission THN102 200/2 vs Placebo
    Statistical analysis description
    Categorical efficacy endpoints – Number of patients in remission (=without residual sleepiness), i.e. ESS < 11 at the end of each treatment period– were analysed using a generalised linear mixed regression model (GLMM), with the treatment, period, treatment by period interaction, sequence, and baseline scores as fixed effects, and the subject nested within sequence as a random effect.
    Comparison groups
    THN102 200/2 v THN102 Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.05332
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    3.0831
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.9842
         upper limit
    9.6577
    Statistical analysis title
    ESS remission THN102 200/18 vs Placebo
    Statistical analysis description
    Categorical efficacy endpoints – Number of patients in remission (=without residual sleepiness), i.e. ESS < 11 at the end of each treatment period– were analysed using a generalised linear mixed regression model (GLMM), with the treatment, period, treatment by period interaction, sequence, and baseline scores as fixed effects, and the subject nested within sequence as a random effect.
    Comparison groups
    THN102 200/18 v THN102 Placebo
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.102
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    2.619
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.8246
         upper limit
    8.3182
    Statistical analysis title
    ESS remission THN102 200/18 vs 200/2
    Statistical analysis description
    Categorical efficacy endpoints – Number of patients in remission (=without residual sleepiness), i.e. ESS < 11 at the end of each treatment period– were analysed using a generalised linear mixed regression model (GLMM), with the treatment, period, treatment by period interaction, sequence, and baseline scores as fixed effects, and the subject nested within sequence as a random effect.
    Comparison groups
    THN102 200/18 v THN102 200/2
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7177
    Method
    Regression, Logistic
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.8495
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.3493
         upper limit
    2.0657

    Secondary: MoCA score analysis

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    End point title
    MoCA score analysis
    End point description
    MoCA score reflects the cognitive capacities of a person. Range of the total score of 10 test items: 0 to 30 points. A high score indicates good cognitive functioning. A score of 26 and above is considered normal.
    End point type
    Secondary
    End point timeframe
    2 weeks
    End point values
    THN102 Placebo THN102 200/2 THN102 200/18
    Number of subjects analysed
    68
    70
    72
    Units: score on a scale
        number (not applicable)
    68
    69
    70
    Statistical analysis title
    MoCA THN102 200/2 vs Placebo
    Statistical analysis description
    Continuous efficacy endpoints – the change from baseline at each key visit (end of treatment period I, II, and III) in ESS, PVT and MoCA - were analysed using a mixed linear regression model, which included the treatment, period, treatment by period interaction, sequence, and baseline scores as fixed effects, and the subject nested within sequence as a random effect.
    Comparison groups
    THN102 200/2 v THN102 Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3815
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.1913
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.6223
         upper limit
    0.2397
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2178
    Statistical analysis title
    MoCA THN102 200/18 vs Placebo
    Statistical analysis description
    Continuous efficacy endpoints – the change from baseline at each key visit (end of treatment period I, II, and III) in ESS, PVT and MoCA - were analysed using a mixed linear regression model, which included the treatment, period, treatment by period interaction, sequence, and baseline scores as fixed effects, and the subject nested within sequence as a random effect.
    Comparison groups
    THN102 200/18 v THN102 Placebo
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.3566
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.2012
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.229
         upper limit
    0.6313
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2174
    Statistical analysis title
    MoCA THN102 200/18 vs 200/2
    Statistical analysis description
    Continuous efficacy endpoints – the change from baseline at each key visit (end of treatment period I, II, and III) in ESS, PVT and MoCA - were analysed using a mixed linear regression model, which included the treatment, period, treatment by period interaction, sequence, and baseline scores as fixed effects, and the subject nested within sequence as a random effect.
    Comparison groups
    THN102 200/18 v THN102 200/2
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0722
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    0.3924
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.0359
         upper limit
    0.8208
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2165

    Secondary: MoCA score

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    End point title
    MoCA score
    End point description
    MoCA score reflects the cognitive capacities of a person. Range of the total score of 10 test items: 0 to 30 points. A high score indicates good cognitive functioning. A score of 26 and above is considered normal.
    End point type
    Secondary
    End point timeframe
    2 weeks
    End point values
    THN102 Placebo THN102 200/2 THN102 200/18
    Number of subjects analysed
    68
    70
    72
    Units: score on a scale
        arithmetic mean (standard deviation)
    28 ± 2.02
    27.8 ± 2.47
    28.2 ± 1.78
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AE collection through study duration, starts with screening until follow up visit (last phone call), a total of 13 weeks.
    Adverse event reporting additional description
    Number of participants with spontaneously reported treatment-related adverse events
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    THN102 placebo
    Reporting group description
    Dosage A

    Reporting group title
    THN102 200/2
    Reporting group description
    Dosage B

    Reporting group title
    THN102 200/9
    Reporting group description
    dosage C

    Serious adverse events
    THN102 placebo THN102 200/2 THN102 200/9
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 72 (0.00%)
    1 / 73 (1.37%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Injury, poisoning and procedural complications
    CONTUSION
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 72 (0.00%)
    1 / 73 (1.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    THN102 placebo THN102 200/2 THN102 200/9
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 68 (4.41%)
    10 / 72 (13.89%)
    22 / 73 (30.14%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 68 (0.00%)
    2 / 72 (2.78%)
    4 / 73 (5.48%)
         occurrences all number
    0
    2
    4
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    2 / 68 (2.94%)
    0 / 72 (0.00%)
    2 / 73 (2.74%)
         occurrences all number
    2
    0
    2
    Chest pain
         subjects affected / exposed
    1 / 68 (1.47%)
    2 / 72 (2.78%)
    1 / 73 (1.37%)
         occurrences all number
    1
    2
    2
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    0 / 68 (0.00%)
    2 / 72 (2.78%)
    3 / 73 (4.11%)
         occurrences all number
    0
    2
    3
    Dry mouth
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 72 (0.00%)
    3 / 73 (4.11%)
         occurrences all number
    0
    0
    3
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 72 (1.39%)
    2 / 73 (2.74%)
         occurrences all number
    0
    1
    2
    Confusional state
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 72 (0.00%)
    2 / 73 (2.74%)
         occurrences all number
    0
    0
    2
    Nightmare
         subjects affected / exposed
    0 / 68 (0.00%)
    0 / 72 (0.00%)
    2 / 73 (2.74%)
         occurrences all number
    0
    0
    2
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    0 / 68 (0.00%)
    2 / 72 (2.78%)
    0 / 73 (0.00%)
         occurrences all number
    0
    2
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 72 (1.39%)
    3 / 73 (4.11%)
         occurrences all number
    0
    1
    3

    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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