Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   44043   clinical trials with a EudraCT protocol, of which   7319   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    An unicenter, open-label, 1-arm, 8-week study to evaluate the efficacy, safety and tolerability of ORY-2001 in aggression in adult population with Adult Attention Deficit Hyperactivity Disorder (ADHD), Borderline Personality Disorder (BPD), Autism Spectrum Disorder (ASD).

    Summary
    EudraCT number
    		 2018-002140-88
    Trial protocol
    		 ES  
    Global end of trial date
    22 Oct 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    08 Aug 2021
    First version publication date
    08 Aug 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CL04-ORY-2001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Oryzon Genomics S.A.
    Sponsor organisation address
    Carrer de Sant Ferran, 74, Oryzon, CORNELLA DE LLOBREGAT, Spain, 08940
    Public contact
    Michael Ropacki, Chief Medical Officer, CNS Clinical & Product Development, Oryzon Genomics S.A., +34 93 515 1313, mropacki@oryzon.com
    Scientific contact
    Michael Ropacki, Chief Medical Officer, CNS Clinical & Product Development, Oryzon Genomics S.A., +34 93 515 1313, mropacki@oryzon.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    22 Oct 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Oct 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the safety, tolerability and efficacy of vafidemstat in adult population with Adult attention deficit hyperactivity disorder (ADHD), Borderline Personality Disorder (BPD) or Autism Spectrum Disorder (ASD)
    Protection of trial subjects
    In accordance with European Union RGPD 2016/679 of 27 April, 2016 the data were processed in accordance with the specifications outlined by the local law to ensure that requirements regarding personal data protection are met. If an external organization processed data on behalf of Oryzon, a contractual procedure was signed between Oryzon and the external organization to ensure compliance with the above-mentioned legislation. If applicable, the participation of patients in this study was reported to the appropriate local data protection agencies, in accordance with European Union RGPD 2016/679 of 27 April 2016 and Country-specific guidelines and laws (Spanish Organic Law 3/2018 of 5 December).
    Background therapy
    		 Patients entered the study under their usual ADHD, BPD or ASD treatment, on a stable dose, for at least 4-months prior to the Screening Visit (until approval of protocol amendment on 19/03/2019) and for at least 1-month prior to the Screening, thereafter. In addition, patients had to remain on this stable treatment dose for their condition (i.e. the patient’s individual maintenance dose for ADHD, BPD or ASD) during the Screening Period and throughout the study.
    Evidence for comparator
    		 N/A
    Actual start date of recruitment
    08 Oct 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
    Spain: 32
    Worldwide total number of subjects
    32
    EEA total number of subjects
    32
    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)
    32
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 A total of 35 subjects were screened to obtain a total of 32 enrolled patients. Recruitment was planned to be equally stratified by disease cohorts. The first 18 patients continued to be distributed as planned and the distribution of the remaining patients was flexible between the three cohorts.

    Pre-assignment
    Screening details
    		 A total of 35 patients were screened at Vall d’Hebron Universitari Hospital. Of those, 3 patients were considered screen failures and therefore discarded. A total of 32 patients were included in the study based on having received at least one dose of the IMP and completed, at least, one study visit.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Adult Attention Deficit Hyperactivity Disorder (ADHD)
    Arm description
    		 Adult Attention Deficit Hyperactivity Disorder (ADHD)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vafidemstat
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Vafidemstat was administered orally, 1.2 mg/day, as a single capsule, fiw, in a 5 days on / 2 days off schedule.

    Arm title
    		 Borderline Personality Disorder (BPD)
    Arm description
    		 Borderline Personality Disorder (BPD)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vafidemstat
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Vafidemstat was administered orally, 1.2 mg/day, as a single capsule, fiw, in a 5 days on / 2 days off schedule.

    Arm title
    		 Autism Spectrum Disorder (ASD)
    Arm description
    		 Autism Spectrum Disorder (ASD)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Vafidemstat
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Vafidemstat was administered orally, 1.2 mg/day, as a single capsule, fiw, in a 5 days on / 2 days off schedule.

    Number of subjects in period 1
    		Adult Attention Deficit Hyperactivity Disorder (ADHD) Borderline Personality Disorder (BPD) Autism Spectrum Disorder (ASD)
    Started
    12
    13
    7
    Completed
    8
    9
    6
    Not completed
    4
    4
    1
         other reasons
    2
    3
    1
         Lost to follow-up
    2
    1
    -

    Baseline characteristics

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

    Reporting group values
    		 Overall trial Total
    Number of subjects
    		 32 32
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 33.12 ± 12.17 -
    Gender categorical
    Units: Subjects
        Female
    		 18 18
        Male
    		 14 14
    Education
    Units: Subjects
        Some school
    		 6 6
        School graduate
    		 17 17
        College graduate
    		 8 8
        University degree
    		 1 1
    Race
    Units: Subjects
        Caucasian
    		 27 27
        Black
    		 0 0
        Asian
    		 0 0
        Latin
    		 5 5
    Height
    Units: meter
        arithmetic mean (standard deviation)
    		 1.7 ± 0.1 -
    Weight
    Units: kilogram(s)
        arithmetic mean (standard deviation)
    		 75.32 ± 23.14 -
    BMI
    Units: kilogram(s)/square meter
        arithmetic mean (standard deviation)
    		 25.86 ± 6.77 -
    Subject analysis sets

    Subject analysis set title
    All groups
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    ADHD, BPD, ASD

    Subject analysis sets values
    		 All groups
    Number of subjects
    32
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    33.12 ± 12.17
    Gender categorical
    Units: Subjects
        Female
    18
        Male
    14
    Education
    Units: Subjects
        Some school
    6
        School graduate
    17
        College graduate
    8
        University degree
    1
    Race
    Units: Subjects
        Caucasian
    27
        Black
    0
        Asian
    0
        Latin
    5
    Height
    Units: meter
        arithmetic mean (standard deviation)
    1.7 ± 0.1
    Weight
    Units: kilogram(s)
        arithmetic mean (standard deviation)
    75.32 ± 23.14
    BMI
    Units: kilogram(s)/square meter
        arithmetic mean (standard deviation)
    25.86 ± 6.77

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Adult Attention Deficit Hyperactivity Disorder (ADHD)
    Reporting group description
    		 Adult Attention Deficit Hyperactivity Disorder (ADHD)

    Reporting group title
    Borderline Personality Disorder (BPD)
    Reporting group description
    		 Borderline Personality Disorder (BPD)

    Reporting group title
    Autism Spectrum Disorder (ASD)
    Reporting group description
    		 Autism Spectrum Disorder (ASD)

    Subject analysis set title
    All groups
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    ADHD, BPD, ASD

    Primary: Number and severity of Treatment Emergent Adverse Events (TEAEs) up to Week 8

    		 Close Top of page
    End point title
    		 Number and severity of Treatment Emergent Adverse Events (TEAEs) up to Week 8 [1]
    End point description
    In the study, all Adverse Events (AEs) were Treatment Emergent Adverse Events (TEAEs) and all the Adverse Reactions (ARs) were Treatment Emergent Adverse Reactions (TEARs).
    End point type
    Primary
    End point timeframe
    From baseline and during the 8-week Treatment Period followed by a 4-week Safety Follow-up Period after the last dose intake of the study drug.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Number of cases, events and percentage of adverse events (AEs), adverse reactions (ARs) and serious ARs were calculated for the entire duration of the study (up to end of follow-up) as aggregated numbers.
    End point values
    		 All groups
    Number of subjects analysed
    32
    Units: number
        Severity - MILD
    96
        Severity - MODERATE
    0
        Severity - SEVERE
    0
    No statistical analyses for this end point

    Primary: Number, frequency and severity of Serious TEAEs up to Week 8

    		 Close Top of page
    End point title
    		 Number, frequency and severity of Serious TEAEs up to Week 8 [2]
    End point description
    End point type
    Primary
    End point timeframe
    From baseline and during the 8-week Treatment Period followed by a 4-week Safety Follow-up Period after the last dose intake of the study drug.
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There were no Serious Adverse Events (SAEs) during the study, up to Visit 7 (Week 8) or the follow-up period
    End point values
    		 All groups
    Number of subjects analysed
    32
    Units: number
    0
    No statistical analyses for this end point

    Primary: Number of withdrawn patients due to TEAEs up to Week 8

    		 Close Top of page
    End point title
    		 Number of withdrawn patients due to TEAEs up to Week 8 [3]
    End point description
    End point type
    Primary
    End point timeframe
    From Baseline and throughout the 8-week Treatment Period.
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: None of the patients withdrew due to safety related events.
    End point values
    		 All groups
    Number of subjects analysed
    32
    Units: number
    0
    No statistical analyses for this end point

    Primary: Physical examination, vital signs and ECG parameters - Change from baseline to Week 8

    		 Close Top of page
    End point title
    		 Physical examination, vital signs and ECG parameters - Change from baseline to Week 8 [4]
    End point description
    End point type
    Primary
    End point timeframe
    Vital signs were measured as part of the physical examination conducted at the Baseline Visit as well as part of the Safety Assessments at each study visit.
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No comparison between groups was performed for this endpoint. The difference between Visit 7(Week 8)/EoS and Visit 1 (Baseline) data was summarized using means, medians, minimum, maximum, standard deviations (SD) and inter-quartile-range. The variations observed were evaluated in terms of "clinically relevant changes".
    End point values
    		 Adult Attention Deficit Hyperactivity Disorder (ADHD) Borderline Personality Disorder (BPD) Autism Spectrum Disorder (ASD) All groups
    Number of subjects analysed
    12
    13
    7
    32
    Units: unit(s)
    arithmetic mean (standard deviation)
        SBP (mm Hg)
    3.25 ± 11.16
    -6.78 ± 9.15
    -3 ± 10.86
    -2.3 ± 10.79
        DBP (mm Hg)
    6.62 ± 12.94
    -3.89 ± 5.4
    -4.5 ± 8.64
    -0.39 ± 10.41
        Supine SBP (mm Hg)
    3.25 ± 11.16
    -6.78 ± 9.15
    -3 ± 10.86
    -2.3 ± 10.79
        Supine DBP (mm Hg)
    6.62 ± 12.94
    -3.89 ± 5.4
    -4.5 ± 8.64
    -0.39 ± 10.41
        HR (bpm)
    2.38 ± 12.25
    -1 ± 15.11
    1.83 ± 6.91
    0.91 ± 12
        Body temperature (°C)
    -0.09 ± 0.22
    -0.06 ± 0.16
    0.02 ± 0.24
    -0.05 ± 0.2
        RR (bpm)
    0.38 ± 1.41
    0.33 ± 2
    0.17 ± 1.17
    0.3 ± 1.55
        Resting RR (bpm)
    0.38 ± 1.41
    0.33 ± 2
    -0.5 ± 1.05
    0.13 ± 1.58
        ECG - HR (bpm)
    2.5 ± 10.62
    -0.33 ± 12.44
    -0.33 ± 4.13
    0.65 ± 9.9
        ECG - PR (ms)
    -4.75 ± 19.09
    -3.33 ± 9.22
    -1.67 ± 6.86
    -3.39 ± 12.61
        ECG - QRS (ms)
    -2.5 ± 7.84
    -1.33 ± 3
    -1.67 ± 3.44
    -1.83 ± 5.08
        ECG - QT (ms)
    -9.5 ± 22.92
    -1.56 ± 26.62
    10 ± 6.07
    -1.3 ± 22.19
        ECG - QTc (ms)
    -0.75 ± 16.53
    -2.33 ± 14.47
    10 ± 17.5
    1.43 ± 16.14
    No statistical analyses for this end point

    Primary: Clinical laboratory parameters - Haematology - Change from baseline to Week 8

    		 Close Top of page
    End point title
    		 Clinical laboratory parameters - Haematology - Change from baseline to Week 8 [5]
    End point description
    End point type
    Primary
    End point timeframe
    At the Baseline Visit as well as part of the Safety Assessments at each study visit.
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No comparison between groups has been performed for this endpoint. The difference between Visit 7(Week 8)/EoS and Visit 1 (Baseline) data was summarized using means, medians, minimum, maximum, standard deviations (SD) and inter-quartile-range. The variations observed were evaluated in terms of "clinically relevant changes".
    End point values
    		 Adult Attention Deficit Hyperactivity Disorder (ADHD) Borderline Personality Disorder (BPD) Autism Spectrum Disorder (ASD) All groups
    Number of subjects analysed
    12
    13
    7
    32
    Units: unit(s)
    arithmetic mean (standard deviation)
        RBC (10e12/L)
    0.07 ± 0.11
    -0.1 ± 0.16
    -0.1 ± 0.24
    -0.04 ± 0.18
        Hb (g/dL)
    -0.01 ± 0.56
    -0.37 ± 0.66
    -0.13 ± 0.48
    -0.18 ± 0.58
        Haematocrit (%)
    0.86 ± 1.21
    -0.38 ± 1.37
    -1.17 ± 2.21
    -0.15 ± 1.71
        MCV (fL)
    0.27 ± 2.26
    1.21 ± 3.13
    -0.68 ± 1.88
    0.39 ± 2.57
        MCH (pg)
    -0.54 ± 0.86
    -0.1 ± 0.96
    0.35 ± 1.01
    -0.13 ± 0.96
        MCHC (g/dL)
    -0.71 ± 0.84
    -0.6 ± 1.81
    0.63 ± 1.17
    -0.32 ± 1.44
        WBC (10e9/L)
    0.42 ± 1.14
    -0.55 ± 1.34
    -1.03 ± 0.69
    -0.33 ± 1.24
        Neutrophils (%)
    -3.44 ± 8.28
    -8.74 ± 12.81
    -7.7 ± 3.91
    -6.63 ± 9.53
        Lymphocytes (%)
    0.74 ± 8.28
    5.24 ± 10.25
    3.35 ± 3.04
    3.18 ± 8.12
        Monocytes (%)
    2.21 ± 1.96
    1.18 ± 1.73
    3.08 ± 3.81
    2.03 ± 2.5
        Eosinophyls (%)
    0.52 ± 2.31
    2.13 ± 2.98
    1.05 ± 0.68
    1.29 ± 2.36
        Basophils (%)
    -0.04 ± 0.15
    0.19 ± 0.21
    0.22 ± 0.2
    0.12 ± 0.22
        Neutrophils (10e9/L)
    -0.12 ± 0.81
    -1.01 ± 1.71
    -1.08 ± 0.5
    0.72 ± 1.24
        Lymphocytes (absolute) (10e9/L)
    0.25 ± 0.75
    0.28 ± 0.55
    -0.07 ± 0.39
    0.18 ± 0.59
        Monocytes (absolute) (10e9/L)
    0.19 ± 0.19
    0.07 ± 0.14
    0.07 ± 0.14
    0.11 ± 0.16
        Eosinophils (absolute) (10e9/L)
    0.09 ± 0.18
    0.16 ± 0.21
    0.07 ± 0.05
    0.11 ± 0.17
        Basophils (absolute) (10e9/L)
    0 ± 0.08
    0.04 ± 0.07
    0.03 ± 0.05
    0.03 ± 0.07
        Platelets (10e9/L)
    -37.5 ± 37.36
    -29.56 ± 49.16
    -29.67 ± 96
    -32.35 ± 58.58
    No statistical analyses for this end point

    Primary: Clinical laboratory parameters - Biochemistry - Change from baseline to Week 8

    		 Close Top of page
    End point title
    		 Clinical laboratory parameters - Biochemistry - Change from baseline to Week 8 [6]
    End point description
    End point type
    Primary
    End point timeframe
    At the Baseline Visit as well as part of the Safety Assessments at each study visit.
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No comparison between groups has been performed for this endpoint. The difference between Visit 7(Week 8)/EoS and Visit 1 (Baseline) data was summarized using means, medians, minimum, maximum, standard deviations (SD) and inter-quartile-range. The variations observed were evaluated in terms of "clinically relevant changes".
    End point values
    		 Adult Attention Deficit Hyperactivity Disorder (ADHD) Borderline Personality Disorder (BPD) Autism Spectrum Disorder (ASD) All groups
    Number of subjects analysed
    12
    13
    7
    32
    Units: unit(s)
    arithmetic mean (standard deviation)
        Glucose (mg/dL)
    -5.12 ± 9.78
    -7.44 ± 13.3
    8 ± 21.23
    -2.61 ± 15.49
        HbA1c (%)
    0 ± 0
    0 ± 0
    -0.2 ± 0
    -0.2 ± 0
        Urea (mg/dL)
    -1 ± 5.26
    -0.11 ± 6.53
    -3.33 ± 4.68
    -1.26 ± 5.57
        Creatinine (mg/dL)
    0.01 ± 0.12
    -0.03 ± 0.09
    0.04 ± 0.07
    0 ± 0.1
        Total bilirubin (mg/dL)
    -0.1 ± 0.21
    0.12 ± 0.31
    -0.01 ± 0.12
    0.01 ± 0.25
        Conjugated bilirubin (mg/dL)
    -0.01 ± 0.04
    0.02 ± 0.06
    0 ± 0.04
    0 ± 0.05
        Sodium (mmol/L)
    -0.69 ± 2.34
    -0.6 ± 3.08
    -0.32 ± 1.18
    -0.56 ± 2.35
        Potassium (mmol/L)
    -0.02 ± 0.21
    0.15 ± 0.39
    0.14 ± 0.1
    0.09 ± 0.28
        Phosphate (mg/dL)
    -0.21 ± 0.7
    -0.33 ± 0.58
    0.05 ± 0.31
    -0.19 ± 0.57
        Calcium (mg/dL)
    -0.23 ± 0.39
    -0.23 ± 0.31
    -0.12 ± 0.23
    -0.2 ± 0.31
        AST (U/L)
    0.88 ± 4.42
    2.89 ± 7.85
    -12 ± 19.6
    -1.7 ± 12.48
        ALT (U/L)
    -3.12 ± 9.08
    1.89 ± 8.24
    -28.5 ± 42.81
    -7.78 ± 25.11
        Alkaline phosphatase (U/L)
    -3.62 ± 6
    4 ± 13.62
    -4.17 ± 5.12
    -0.78 ± 10.01
        GGT (U/L)
    1.62 ± 5.13
    4.56 ± 8.44
    -1.5 ± 6.35
    1.96 ± 7.04
        Creatinine kinase (U/L)
    -31 ± 96.19
    -60.57 ± 164.24
    -26.75 ± 38.45
    -42.88 ± 117.54
        LDH (U/L)
    90 ± 103.41
    30.86 ± 90.02
    3.75 ± 144.35
    35.79 ± 105.84
        Amylase (U/L)
    1.6 ± 10.55
    -0.29 ± 9.32
    -10.75 ± 6.24
    -2.31 ± 9.91
        Cholesterol (mg/dL)
    -12.5 ± 37.06
    -8 ± 28.4
    -21.83 ± 8.3
    -13.17 ± 27.89
        Triglycerides (mg/dL)
    -23.25 ± 28.28
    1.56 ± 9.74
    -33.83 ± 89.76
    -16.3 ± 48.5
        Total protein (g/dL)
    -0.01 ± 0.35
    -0.1 ± 0.4
    -0.2 ± 0.24
    -0.1 ± 0.34
        Albumin (g/dL)
    0.03 ± 0.18
    -0.09 ± 0.26
    -0.03 ± 0.14
    -0.05 ± 0.2
        CRP (mg/dL)
    0.31 ± 0.47
    0.02 ± 0.39
    -0.04 ± 0.11
    0.1 ± 0.38
    No statistical analyses for this end point

    Primary: Use of concomitant medication throughout the study period

    		 Close Top of page
    End point title
    		 Use of concomitant medication throughout the study period [7]
    End point description
    End point type
    Primary
    End point timeframe
    Since Screening Period for up to 1 week and an 8-week Treatment Period followed by a 4-week Safety Follow-up Period after the last dose intake of the study drug.
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses has been applied to this endpoint
    End point values
    		 All groups
    Number of subjects analysed
    32
    Units: number
        AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
    1
        ANALGESICS
    15
        ANTIBACTERIALS FOR SYSTEMIC USE
    2
        ANTIBIOTICS AND CHEMOTHERAPEUTICS FOR DERMATOLOGIC
    1
        ANTIEPILEPTICS
    11
        ANTIHISTAMINES FOR SYSTEMIC USE
    3
        ANTIHYPERTENSIVES
    1
        ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS
    11
        COUGH AND COLD PREPARATIONS
    1
        DRUGS USED IN DIABETES
    1
        LIPID MODIFYING AGENTS
    1
        MINERAL SUPPLEMENTS
    1
        MUSCLE RELAXANTS
    1
        PSYCHOANALEPTICS
    16
        PSYCHOLEPTICS
    15
        SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
    1
        TONICS
    1
    No statistical analyses for this end point

    Secondary: Neuropsychiatric Inventory Questionnaire - Agitation/Aggression (NPI-A/A) - Change from Baseline to Week 8

    		 Close Top of page
    End point title
    		 Neuropsychiatric Inventory Questionnaire - Agitation/Aggression (NPI-A/A) - Change from Baseline to Week 8
    End point description
    Change from Visit 1 (Baseline) to Visit 7/EoS (Week 8) was calculated, for each patient, for all groups (aggregated data) and the different groups (cohorts), as the difference between Visit 7 (Week 8)/EoS and Visit 1 (Baseline) in the PPS population. Results were presented as score’s mean values and standard deviation (SD) wit p-values calculated as Wilcoxon Sign-rank Test. After 8 weeks of treatment the difference between Visit 7/EoS and Visit 1 (Baseline) for the NPI-A/A for all groups (aggregated data), was statistically significant (p<0.0001). There was also a statistically significant difference in NPI-A/A score after 8 weeks of treatment with vafidemstat for each of the different cohorts (ADHD, BPD and ADS), with p-values being p=0.007, p=0.0068 and p=0.0175, respectively.
    End point type
    Secondary
    End point timeframe
    From Visit 1 (Baseline) to Visit 7(Week 8)/EoS
    End point values
    		 Adult Attention Deficit Hyperactivity Disorder (ADHD) Borderline Personality Disorder (BPD) Autism Spectrum Disorder (ASD) All groups
    Number of subjects analysed
    8
    9
    6
    23
    Units: unit(s)
        arithmetic mean (standard deviation)
    -3.88 ± 1.55
    -2.78 ± 1.64
    -2.67 ± 1.21
    -3.13 ± 1.55
    No statistical analyses for this end point

    Secondary: Neuropsychiatric Inventory Questionnaire (NPI) - Total NPI - Change from Baseline to Week 8

    		 Close Top of page
    End point title
    		 Neuropsychiatric Inventory Questionnaire (NPI) - Total NPI - Change from Baseline to Week 8
    End point description
    Change from Visit 1 (Baseline) to Visit 7/EoS (Week 8) was calculated, for each patient, for all groups (aggregated data) and the different groups (cohorts), as the difference between Visit 7 (Week 8)/EoS and Visit 1 (Baseline) in the PPS population. Results were presented as score’s mean values, standard deviation (SD) and p-values calculated as Wilcoxon Sign-rank Test. After 8 weeks of treatment, the difference between Visit 7/EoS and Visit 1 (Baseline) for the Total NPI score for all groups (aggregated data), was statistically significant (p<0.0001). After 8 weeks of treatment, there was a statistically significant difference in the Total NPI for each of the cohorts: p=0.0065 for ADHD; p=0.0124 for BPD; and p=0.0178 for ASD.
    End point type
    Secondary
    End point timeframe
    From Visit 1 (Baseline) to Visit 7(Week 8)/EoS
    End point values
    		 Adult Attention Deficit Hyperactivity Disorder (ADHD) Borderline Personality Disorder (BPD) Autism Spectrum Disorder (ASD) All groups
    Number of subjects analysed
    8
    9
    6
    23
    Units: unit(s)
        arithmetic mean (standard deviation)
    -4.88 ± 1.89
    -5.56 ± 5.13
    -6 ± 2.53
    -5.43 ± 3.51
    No statistical analyses for this end point

    Secondary: Clinical Global Impression of Severity (CGI-S) aggression scale - Change from Baseline to Week 8

    		 Close Top of page
    End point title
    		 Clinical Global Impression of Severity (CGI-S) aggression scale - Change from Baseline to Week 8
    End point description
    Change from Visit 1 (Baseline) to Visit 7/EoS (Week 8) was calculated, for each patient, for all groups (aggregated data) and the different groups (cohorts), as the difference between Visit 7 (Week 8)/EoS and Visit 1 (Baseline) in the PPS population. Results were presented as score’s mean values and standard deviation (SD) wit p-values calculated as Wilcoxon Sign-rank Test. After 8 weeks of treatment the difference between Visit 7/EoS and Visit 1 (Baseline) in the CGI-S score for all groups (aggregated data) was statistically significant (p<0.0001). There was also a statistically significant difference after 8 weeks of treatment with vafidemstat for each of the different cohorts (ADHD, BPD and ADS); p-values: p=0.0066, p=0.0064 and p=0.016, respectively.
    End point type
    Secondary
    End point timeframe
    From Visit 1 (Baseline) to Visit 7(Week 8)/EoS
    End point values
    		 Adult Attention Deficit Hyperactivity Disorder (ADHD) Borderline Personality Disorder (BPD) Autism Spectrum Disorder (ASD) All groups
    Number of subjects analysed
    8
    9
    6
    23
    Units: unit(s)
        arithmetic mean (standard deviation)
    -1.88 ± 0.83
    -1.78 ± 0.97
    -1.5 ± 0.55
    -1.74 ± 0.81
    No statistical analyses for this end point

    Secondary: Clinical Global Impression of Improvements (CGI-I) aggression scale - Change from Baseline to Week 8

    		 Close Top of page
    End point title
    		 Clinical Global Impression of Improvements (CGI-I) aggression scale - Change from Baseline to Week 8
    End point description
    Change from Visit 1 (Baseline) to Visit 7/EoS (Week 8) was calculated, for each patient, for all groups (aggregated data) and the different groups (cohorts), as the difference between Visit 7 (Week 8)/EoS and Visit 1 (Baseline) in the PPS population. Results were presented as score’s mean values and standard deviation (SD) wit p-values calculated as Wilcoxon Sign-rank Test. After 8 weeks of treatment the difference between Visit 7/EoS and Visit 1 (Baseline) in the CGI-I score for all groups (aggregated data) was statistically significant (p<0.0001). There was also a statistically significant difference after 8 weeks of treatment with vafidemstat for each of the different cohorts (ADHD, BPD and ADS); p-values: p=0.0066, p=0.0155 and p=0.016, respectively.
    End point type
    Secondary
    End point timeframe
    From Visit 1 (Baseline) to Visit 7(Week 8)/EoS
    End point values
    		 Adult Attention Deficit Hyperactivity Disorder (ADHD) Borderline Personality Disorder (BPD) Autism Spectrum Disorder (ASD) All groups
    Number of subjects analysed
    8
    8
    6
    22
    Units: unit(s)
        arithmetic mean (standard deviation)
    -2.12 ± 0.83
    -1.5 ± 1.07
    -2.5 ± 0.55
    -2 ± 0.93
    No statistical analyses for this end point

    Secondary: Attention Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS) - Changes from baseline to Week 8

    		 Close Top of page
    End point title
    		 Attention Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS) - Changes from baseline to Week 8 [8]
    End point description
    Change from Visit 1 (Baseline) to Visit 7/EoS (Week 8) was calculated, for each patient, in the ADHD group (cohort), as the difference between Visit 7 (Week 8)/EoS and Visit 1 (Baseline) in the PPS population. Results were presented as score’s mean values and standard deviation (SD) wit p-values calculated as Wilcoxon Sign-rank Test. The difference between Visit 7/EoS and Visit 1 (Baseline) in the ADHD-RS score, after 8 weeks of treatment with vafidemstat, was statistically significant (p=0.0496).
    End point type
    Secondary
    End point timeframe
    From Visit 1 (Baseline) to Visit 7 (Week 8)/EoS
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: ADHD patients only
    End point values
    		 Adult Attention Deficit Hyperactivity Disorder (ADHD)
    Number of subjects analysed
    8
    Units: unit(s)
        arithmetic mean (standard deviation)
    -5 ± 7.45
    No statistical analyses for this end point

    Secondary: Borderline Personality Disease Checklist (BPDCL) - Change from Baseline to Week 8

    		 Close Top of page
    End point title
    		 Borderline Personality Disease Checklist (BPDCL) - Change from Baseline to Week 8 [9]
    End point description
    Change from Visit 1 (Baseline) to Visit 7/EoS (Week 8) was calculated, for each patient, in the BPD group (cohort), as the difference between Visit 7 (Week 8)/EoS and Visit 1 (Baseline) in the PPS population. Results were presented as score’s mean values and standard deviation (SD) wit p-values calculated as Wilcoxon Sign-rank Test. The difference between Visit 7/EoS and Visit 1 (Baseline) in the BPDCL Total score, after 8 weeks of treatment with vafidemstat, was statistically significant (p=0.0022).
    End point type
    Secondary
    End point timeframe
    From Visit 1 (Baseline) to Visit 7 (Week 8)/EoS
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: BPD patients only
    End point values
    		 Borderline Personality Disorder (BPD)
    Number of subjects analysed
    9
    Units: unit(s)
        arithmetic mean (standard deviation)
    -38.56 ± 29.5
    No statistical analyses for this end point

    Other pre-specified: Pharmacokinetics: trough vafidemstat plasma levels (Ctrough) on Days 1, 5, and 26 (Visit 1, 2 and 5)

    		 Close Top of page
    End point title
    		 Pharmacokinetics: trough vafidemstat plasma levels (Ctrough) on Days 1, 5, and 26 (Visit 1, 2 and 5)
    End point description
    Descriptive summary statistics of the Ctrough values observed in all groups (aggregated data) and the different cohorts was conducted (shown below). There were no statistically significant differences among the Ctrough values observed for each of the different cohorts (ADHD, BPD and ADS) during the course of the study, nor there were on day 5 and 26 (Wilcoxon Sign-rank Test), suggesting that steady state concentrations were reached within the first week of treatment in all cases.
    End point type
    Other pre-specified
    End point timeframe
    Days 1, 5, and 26 (Visit 1, Visit 2, and Visit 5)
    End point values
    		 Adult Attention Deficit Hyperactivity Disorder (ADHD) Borderline Personality Disorder (BPD) Autism Spectrum Disorder (ASD) All groups
    Number of subjects analysed
    11
    12
    7
    30
    Units: unit(s)
    arithmetic mean (standard deviation)
        Day 1
    0.00 ± 0.00
    0.00 ± 0.00
    0.00 ± 0.00
    0.00 ± 0.00
        Day 5
    4127.13 ± 2102.36
    5279.92 ± 3681.31
    7321.89 ± 7699.89
    5378.70 ± 4819.95
        Day 26
    4566.84 ± 3386.00
    3767.58 ± 2363.21
    7121.25 ± 8838.12
    4892.17 ± 5199.39
    No statistical analyses for this end point

    Other pre-specified: Pharmacodynamics: Change over time in LSD1 target engagement (TE) in PBMCs on Days 1, 5, and 26 (Visit 1, 2 and 5)

    		 Close Top of page
    End point title
    		 Pharmacodynamics: Change over time in LSD1 target engagement (TE) in PBMCs on Days 1, 5, and 26 (Visit 1, 2 and 5)
    End point description
    A descriptive summary of the LSD1-TE values observed in all groups and the different cohorts is shown below. There were no statistically significant differences among the LSD1-TE values observed for each of the different cohorts (ADHD, BPD and ADS) during the course of the study, nor there were on day 5 and 26 (Wilcoxon Sign-rank Test), suggesting that the maximum effect was reached within the first week of treatment in all patients.
    End point type
    Other pre-specified
    End point timeframe
    Days 1, 5, and 26 (Visit 1, Visit 2, and Visit 5)
    End point values
    		 Adult Attention Deficit Hyperactivity Disorder (ADHD) Borderline Personality Disorder (BPD) Autism Spectrum Disorder (ASD) All groups
    Number of subjects analysed
    10
    11
    7
    28
    Units: unit(s)
    arithmetic mean (standard deviation)
        Day 1
    0.00 ± 0.00
    0.00 ± 0.00
    0.00 ± 0.00
    0.00 ± 0.00
        Day 5
    75.01 ± 9.46
    76.65 ± 4.63
    68.13 ± 16.52
    73.67 ± 11.35
        Day 26
    71.92 ± 12.60
    61.96 ± 26.69
    75.60 ± 10.98
    68.98 ± 19.98
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Throughout the study period
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    All groups
    Reporting group description
    		 ADHD, BPD, ASD

    Serious adverse events
    		 All groups
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 32 (0.00%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 All groups
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    24 / 32 (75.00%)
    Investigations
    Blood creatine phosphokinase abnormal
         subjects affected / exposed
    3 / 32 (9.38%)
         occurrences all number
    3
    Platelet count decreased
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Electrocardiogram QT interval abnormal
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Amylase abnormal
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Blood lactate dehydrogenase abnormal
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Injury, poisoning and procedural complications
    Overdose
         subjects affected / exposed
    2 / 32 (6.25%)
         occurrences all number
    6
    Poisoning
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Toxicity to various agents
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 32 (6.25%)
         occurrences all number
    2
    Surgical and medical procedures
    Female sterilisation
         subjects affected / exposed [1]
    1 / 18 (5.56%)
         occurrences all number
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    10 / 32 (31.25%)
         occurrences all number
    26
    Sensory disturbance
         subjects affected / exposed
    2 / 32 (6.25%)
         occurrences all number
    2
    Somnolence
         subjects affected / exposed
    2 / 32 (6.25%)
         occurrences all number
    2
    Presyncope
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    General disorders and administration site conditions
    Discomfort
         subjects affected / exposed
    2 / 32 (6.25%)
         occurrences all number
    3
    Fatigue
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Pyrexia
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    2 / 32 (6.25%)
         occurrences all number
    2
    Abdominal pain
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Dry mouth
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Diarrhoea
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    4 / 32 (12.50%)
         occurrences all number
    7
    Insomnia
         subjects affected / exposed
    2 / 32 (6.25%)
         occurrences all number
    4
    Abnormal behaviour
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    2
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 32 (6.25%)
         occurrences all number
    2
    Muscle contracture
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Myalgia
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Pain in extremity
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Infections and infestations
    Influenza
         subjects affected / exposed
    8 / 32 (25.00%)
         occurrences all number
    9
    Nasopharyngitis
         subjects affected / exposed
    4 / 32 (12.50%)
         occurrences all number
    4
    Oral herpes
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Herpes virus infection
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Bronchitis
         subjects affected / exposed
    1 / 32 (3.13%)
         occurrences all number
    1
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The study included 18 female subjects

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Mar 2019
    The study was designed to study the effect of vafidemstat on aggression across 5 different CNS conditions (ADHD, BPD, ASD, AD and DLB). After the protocol amendment approval, the AD and DLB cohorts were dropped for lack of recruitment.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA