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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42769   clinical trials with a EudraCT protocol, of which   7044   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    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:
    Open-Label Safety Study of ADS-5102 (Amantadine HCl) Extended Release Capsules for the Treatment of Levodopa-Induced Dyskinesia

    Summary
    EudraCT number
    2014-003739-20
    Trial protocol
    DE   ES   AT   FR  
    Global end of trial date
    28 Feb 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    15 Mar 2019
    First version publication date
    15 Mar 2019
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    ADS-AMT-PD302
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02202551
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Adamas Pharmaceuticals, Inc.
    Sponsor organisation address
    1900 Powell Street, Suite 1000, Emeryville,, California, United States, 94608
    Public contact
    Dorothy Engelking, Adamas Pharmaceuticals, Inc., 510 4503551, dengelking@adamaspharma.com
    Scientific contact
    Dorothy Engelking, Adamas Pharmaceuticals, Inc., 510 4503551, dengelking@adamaspharma.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
    14 Sep 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Feb 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Feb 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the safety and tolerability of ADS-5102 oral capsules, an extended release formulation of amantadine, administered at a dose of 340 mg once nightly at bedtime for the treatment of levodopa induced dyskinesia (LID) in subjects with Parkinson's disease (PD).
    Protection of trial subjects
    This study was conducted in compliance with Good Clinical Practice (GCP) according to the United States (US) Code of Federal Regulations (CFR) governing the protection of human subjects (21 CFR 50), IRB, REB, or IEC (21 CFR 56), the obligations of clinical investigators (21 CFR 312), International Conference for Harmonisation GCP guidelines, and with the ethical principles originating in the Declaration of Helsinki. Written informed consent was obtained from all study subjects before any study-related procedures were performed. The investigator or designee fully explained, in layman’s terms, the nature of the study, along with the aims, methods, potential risks, and any discomfort that participation may entail, as well as insurance and other procedures for compensation in case of injury. The investigator explained that the study was for research purposes only and that therapeutic benefit to the subject may not have been an outcome of participation. The investigator also explained that subjects were completely free to refuse to enter the study or to withdraw from it at any time without prejudice. Each subject acknowledged receipt of this information by giving written informed consent (i.e., signing the ICF) for participation in the study.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    28 Jul 2014
    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: 9
    Country: Number of subjects enrolled
    Austria: 3
    Country: Number of subjects enrolled
    France: 29
    Country: Number of subjects enrolled
    Germany: 30
    Country: Number of subjects enrolled
    United States: 152
    Worldwide total number of subjects
    223
    EEA total number of subjects
    71
    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)
    109
    From 65 to 84 years
    114
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    -

    Pre-assignment period milestones
    Number of subjects started
    223
    Number of subjects completed
    223

    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
    Group 1A
    Arm description
    Subjects who completed an Adamas efficacy study evaluating ADS-5102 in LID (and received ADS-5102) and chose to immediately transition into the current study without a time gap.
    Arm type
    Experimental

    Investigational medicinal product name
    ADS-5102 capsules
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received a daily ADS-5102 dose of 170 mg (1 ADS-5102-containing capsule) during the first week of treatment, 340 mg (2 ADS-5102 capsules) during Weeks 2 through 100, and 170 mg (1 ADS-5102 capsule) during the last week of treatment. Study drug was to be taken once daily at bedtime (if possible, no earlier than 9 pm). Capsules were to be swallowed intact, and were to be taken with any nonalcoholic beverage, with or without food.

    Arm title
    Group 1P
    Arm description
    Subjects who completed an Adamas efficacy study evaluating ADS-5102 in LID (and received placebo) and chose to immediately transition into the current study without a time gap.
    Arm type
    Experimental

    Investigational medicinal product name
    ADS-5102 capsules
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received a daily ADS-5102 dose of 170 mg (1 ADS-5102-containing capsule) during the first week of treatment, 340 mg (2 ADS-5102 capsules) during Weeks 2 through 100, and 170 mg (1 ADS-5102 capsule) during the last week of treatment. Study drug was to be taken once daily at bedtime (if possible, no earlier than 9 pm). Capsules were to be swallowed intact, and were to be taken with any nonalcoholic beverage, with or without food.

    Arm title
    Group 2
    Arm description
    Subjects who completed a previous Adamas efficacy study evaluating ADS-5102 in LID and entered the current study with a time gap
    Arm type
    Experimental

    Investigational medicinal product name
    ADS-5102 capsules
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received a daily ADS-5102 dose of 170 mg (1 ADS-5102-containing capsule) during the first week of treatment, 340 mg (2 ADS-5102 capsules) during Weeks 2 through 100, and 170 mg (1 ADS-5102 capsule) during the last week of treatment. Study drug was to be taken once daily at bedtime (if possible, no earlier than 9 pm). Capsules were to be swallowed intact, and were to be taken with any nonalcoholic beverage, with or without food.

    Arm title
    Group 3
    Arm description
    Subjects who would have been deemed ineligible for participation in a previous Adamas efficacy study due to having undergone deep brain stimulation (DBS).
    Arm type
    Experimental

    Investigational medicinal product name
    ADS-5102 capsules
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received a daily ADS-5102 dose of 170 mg (1 ADS-5102-containing capsule) during the first week of treatment, 340 mg (2 ADS-5102 capsules) during Weeks 2 through 100, and 170 mg (1 ADS-5102 capsule) during the last week of treatment. Study drug was to be taken once daily at bedtime (if possible, no earlier than 9 pm). Capsules were to be swallowed intact, and were to be taken with any nonalcoholic beverage, with or without food.

    Number of subjects in period 1
    Group 1A Group 1P Group 2 Group 3
    Started
    60
    78
    24
    61
    Completed
    35
    41
    14
    39
    Not completed
    25
    37
    10
    22
         Sponsor's decision
    3
    -
    -
    -
         Other
    11
    8
    3
    5
         Subject unwilling to proceed
    1
    6
    2
    4
         Consent withdrawn by subject
    -
    3
    1
    2
         Lost to follow-up
    -
    1
    1
    1
         Subject discontinued study drug
    10
    19
    3
    10

    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
    223 223
    Age categorical
    Units: Subjects
        In utero
    0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0
        Newborns (0-27 days)
    0 0
        Infants and toddlers (28 days-23 months)
    0 0
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    109 109
        From 65-84 years
    114 114
        85 years and over
    0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    63.7 ± 9.32 -
    Gender categorical
    Units: Subjects
        Female
    92 92
        Male
    131 131

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Group 1A
    Reporting group description
    Subjects who completed an Adamas efficacy study evaluating ADS-5102 in LID (and received ADS-5102) and chose to immediately transition into the current study without a time gap.

    Reporting group title
    Group 1P
    Reporting group description
    Subjects who completed an Adamas efficacy study evaluating ADS-5102 in LID (and received placebo) and chose to immediately transition into the current study without a time gap.

    Reporting group title
    Group 2
    Reporting group description
    Subjects who completed a previous Adamas efficacy study evaluating ADS-5102 in LID and entered the current study with a time gap

    Reporting group title
    Group 3
    Reporting group description
    Subjects who would have been deemed ineligible for participation in a previous Adamas efficacy study due to having undergone deep brain stimulation (DBS).

    Primary: Adverse events

    Close Top of page
    End point title
    Adverse events [1]
    End point description
    End point type
    Primary
    End point timeframe
    From start of dosing to end of study.
    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: Per protocol there were no statistical analyses conducted for this end point.
    End point values
    Group 1A Group 1P Group 2 Group 3
    Number of subjects analysed
    60
    78
    24
    61
    Units: Subjects
        Adverse Events
    57
    70
    23
    55
        Study drug-related adverse events
    31
    45
    16
    32
        Serious adverse events
    16
    21
    6
    17
        Study drug-related serious adverse events
    1
    3
    0
    1
        Permanently discontinued IMP due to AE
    12
    21
    6
    10
        Permanently discontinued IMP due to related AE
    4
    15
    4
    8
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From start of dosing to end of study.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Group 1A
    Reporting group description
    Subjects who completed an Adamas efficacy study evaluating ADS-5102 in LID (and received ADS-5102) and chose to immediately transition into the current study without a time gap.

    Reporting group title
    Group 1P
    Reporting group description
    Subjects who completed an Adamas efficacy study evaluating ADS-5102 in LID (and received placebo) and chose to immediately transition into the current study without a time gap.

    Reporting group title
    Group 2
    Reporting group description
    Subjects who completed a previous Adamas efficacy study evaluating ADS-5102 in LID and entered the current study with a time gap

    Reporting group title
    Group 3
    Reporting group description
    Subjects who would have been deemed ineligible for participation in a previous Adamas efficacy study due to having undergone deep brain stimulation (DBS).

    Serious adverse events
    Group 1A Group 1P Group 2 Group 3
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 60 (26.67%)
    21 / 78 (26.92%)
    6 / 24 (25.00%)
    17 / 61 (27.87%)
         number of deaths (all causes)
    4
    2
    2
    1
         number of deaths resulting from adverse events
    4
    2
    2
    1
    Vascular disorders
    Hypertensive crisis
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    1 / 24 (4.17%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Abasia
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Psychotic disorder
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    1 / 24 (4.17%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mania
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    1 / 24 (4.17%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Laceration
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 60 (1.67%)
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic fracture
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acetabulum fracture
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Confusion postoperative
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    1 / 24 (4.17%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Forearm fracture
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive cardiomyopathy
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory arrest
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    1 / 24 (4.17%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Encephalopathy
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neuroleptic malignant syndrome
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parkinson's disease
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    3 / 61 (4.92%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    On and off phenomenon
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Restless legs syndrome
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokinesia
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intercostal neuralgia
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyskinesia
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo positional
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Volvulus
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colonic pseudo-obstruction
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteonecrosis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    1 / 24 (4.17%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint effusion
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Clostridium difficile sepsis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pseudomonal sepsis
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    1 / 24 (4.17%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Staphylococcus sepsis
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    1 / 24 (4.17%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    1 / 24 (4.17%)
    0 / 61 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    1 / 24 (4.17%)
    1 / 61 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Group 1A Group 1P Group 2 Group 3
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    57 / 60 (95.00%)
    70 / 78 (89.74%)
    23 / 24 (95.83%)
    55 / 61 (90.16%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 60 (3.33%)
    6 / 78 (7.69%)
    0 / 24 (0.00%)
    4 / 61 (6.56%)
         occurrences all number
    2
    6
    0
    4
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 60 (0.00%)
    4 / 78 (5.13%)
    1 / 24 (4.17%)
    1 / 61 (1.64%)
         occurrences all number
    0
    4
    1
    1
    General disorders and administration site conditions
    Oedema peripheral
         subjects affected / exposed
    10 / 60 (16.67%)
    12 / 78 (15.38%)
    2 / 24 (8.33%)
    12 / 61 (19.67%)
         occurrences all number
    10
    12
    2
    12
    Psychiatric disorders
    Hallucination (pooled)
    Additional description: The Hallucinations (Pooled) term combines all Preferred Terms that contain the term "Hallucination".
         subjects affected / exposed
    15 / 60 (25.00%)
    24 / 78 (30.77%)
    5 / 24 (20.83%)
    10 / 61 (16.39%)
         occurrences all number
    15
    24
    5
    10
    Hallucination, visual
         subjects affected / exposed
    14 / 60 (23.33%)
    24 / 78 (30.77%)
    4 / 24 (16.67%)
    10 / 61 (16.39%)
         occurrences all number
    14
    24
    4
    10
    Insomnia
         subjects affected / exposed
    8 / 60 (13.33%)
    5 / 78 (6.41%)
    4 / 24 (16.67%)
    4 / 61 (6.56%)
         occurrences all number
    8
    5
    4
    4
    Depression
         subjects affected / exposed
    4 / 60 (6.67%)
    5 / 78 (6.41%)
    2 / 24 (8.33%)
    4 / 61 (6.56%)
         occurrences all number
    4
    5
    2
    4
    Anxiety
         subjects affected / exposed
    3 / 60 (5.00%)
    6 / 78 (7.69%)
    1 / 24 (4.17%)
    4 / 61 (6.56%)
         occurrences all number
    3
    6
    1
    4
    Abnormal dreams
         subjects affected / exposed
    5 / 60 (8.33%)
    4 / 78 (5.13%)
    2 / 24 (8.33%)
    2 / 61 (3.28%)
         occurrences all number
    5
    4
    2
    2
    Rapid eye movements sleep abnormal
         subjects affected / exposed
    1 / 60 (1.67%)
    4 / 78 (5.13%)
    3 / 24 (12.50%)
    3 / 61 (4.92%)
         occurrences all number
    1
    4
    3
    3
    Confusional state
         subjects affected / exposed
    2 / 60 (3.33%)
    3 / 78 (3.85%)
    3 / 24 (12.50%)
    2 / 61 (3.28%)
         occurrences all number
    2
    3
    3
    2
    Sleep disorder
         subjects affected / exposed
    1 / 60 (1.67%)
    6 / 78 (7.69%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences all number
    1
    6
    0
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    13 / 60 (21.67%)
    29 / 78 (37.18%)
    8 / 24 (33.33%)
    23 / 61 (37.70%)
         occurrences all number
    13
    29
    8
    23
    Contusion
         subjects affected / exposed
    4 / 60 (6.67%)
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    4
    2
    0
    1
    Laceration
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences all number
    3
    1
    0
    0
    Wrist fracture
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    2 / 24 (8.33%)
    0 / 61 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Head injury
         subjects affected / exposed
    3 / 60 (5.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Investigations
    Weight decreased
         subjects affected / exposed
    4 / 60 (6.67%)
    4 / 78 (5.13%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    4
    4
    0
    1
    Glomerular filtration rate decreased
         subjects affected / exposed
    2 / 60 (3.33%)
    4 / 78 (5.13%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    2
    4
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    3 / 60 (5.00%)
    2 / 78 (2.56%)
    2 / 24 (8.33%)
    1 / 61 (1.64%)
         occurrences all number
    3
    2
    2
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    4 / 60 (6.67%)
    10 / 78 (12.82%)
    5 / 24 (20.83%)
    3 / 61 (4.92%)
         occurrences all number
    4
    10
    5
    3
    On and off phenomenon
         subjects affected / exposed
    7 / 60 (11.67%)
    4 / 78 (5.13%)
    4 / 24 (16.67%)
    3 / 61 (4.92%)
         occurrences all number
    7
    4
    4
    3
    Parkinson's disease
         subjects affected / exposed
    3 / 60 (5.00%)
    5 / 78 (6.41%)
    1 / 24 (4.17%)
    6 / 61 (9.84%)
         occurrences all number
    3
    5
    1
    6
    Cognitive disorder
         subjects affected / exposed
    2 / 60 (3.33%)
    2 / 78 (2.56%)
    3 / 24 (12.50%)
    0 / 61 (0.00%)
         occurrences all number
    2
    2
    3
    0
    Balance disorder
         subjects affected / exposed
    0 / 60 (0.00%)
    2 / 78 (2.56%)
    3 / 24 (12.50%)
    1 / 61 (1.64%)
         occurrences all number
    0
    2
    3
    1
    Syncope
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 78 (1.28%)
    1 / 24 (4.17%)
    1 / 61 (1.64%)
         occurrences all number
    3
    1
    1
    1
    Headache
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    2 / 24 (8.33%)
    1 / 61 (1.64%)
         occurrences all number
    1
    0
    2
    1
    Somnolence
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 78 (0.00%)
    1 / 24 (4.17%)
    4 / 61 (6.56%)
         occurrences all number
    0
    0
    1
    4
    Eye disorders
    Cataract
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 78 (1.28%)
    1 / 24 (4.17%)
    0 / 61 (0.00%)
         occurrences all number
    3
    1
    1
    0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    9 / 60 (15.00%)
    12 / 78 (15.38%)
    6 / 24 (25.00%)
    3 / 61 (4.92%)
         occurrences all number
    9
    12
    6
    3
    Nausea
         subjects affected / exposed
    7 / 60 (11.67%)
    8 / 78 (10.26%)
    6 / 24 (25.00%)
    1 / 61 (1.64%)
         occurrences all number
    7
    8
    6
    1
    Dry mouth
         subjects affected / exposed
    4 / 60 (6.67%)
    6 / 78 (7.69%)
    4 / 24 (16.67%)
    3 / 61 (4.92%)
         occurrences all number
    4
    6
    4
    3
    Vomiting
         subjects affected / exposed
    1 / 60 (1.67%)
    2 / 78 (2.56%)
    3 / 24 (12.50%)
    2 / 61 (3.28%)
         occurrences all number
    1
    2
    3
    2
    Gastrooesophageal reflux disease
         subjects affected / exposed
    3 / 60 (5.00%)
    0 / 78 (0.00%)
    2 / 24 (8.33%)
    2 / 61 (3.28%)
         occurrences all number
    3
    0
    2
    2
    Abdominal pain
         subjects affected / exposed
    3 / 60 (5.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 61 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    2 / 60 (3.33%)
    4 / 78 (5.13%)
    1 / 24 (4.17%)
    0 / 61 (0.00%)
         occurrences all number
    2
    4
    1
    0
    Skin and subcutaneous tissue disorders
    Livedo reticularis
         subjects affected / exposed
    6 / 60 (10.00%)
    5 / 78 (6.41%)
    3 / 24 (12.50%)
    6 / 61 (9.84%)
         occurrences all number
    6
    5
    3
    6
    Dry skin
         subjects affected / exposed
    0 / 60 (0.00%)
    1 / 78 (1.28%)
    2 / 24 (8.33%)
    1 / 61 (1.64%)
         occurrences all number
    0
    1
    2
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    4 / 60 (6.67%)
    5 / 78 (6.41%)
    2 / 24 (8.33%)
    4 / 61 (6.56%)
         occurrences all number
    4
    5
    2
    4
    Arthralgia
         subjects affected / exposed
    5 / 60 (8.33%)
    5 / 78 (6.41%)
    1 / 24 (4.17%)
    1 / 61 (1.64%)
         occurrences all number
    5
    5
    1
    1
    Pain in extremity
         subjects affected / exposed
    4 / 60 (6.67%)
    1 / 78 (1.28%)
    1 / 24 (4.17%)
    4 / 61 (6.56%)
         occurrences all number
    4
    1
    1
    4
    Osteoarthritis
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    3 / 61 (4.92%)
         occurrences all number
    3
    1
    0
    3
    Muscle spasms
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 78 (0.00%)
    1 / 24 (4.17%)
    4 / 61 (6.56%)
         occurrences all number
    1
    0
    1
    4
    Metabolism and nutrition disorders
    Vitamin B12 deficiency
         subjects affected / exposed
    3 / 60 (5.00%)
    0 / 78 (0.00%)
    1 / 24 (4.17%)
    1 / 61 (1.64%)
         occurrences all number
    3
    0
    1
    1
    Vitamin D deficiency
         subjects affected / exposed
    3 / 60 (5.00%)
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    1 / 61 (1.64%)
         occurrences all number
    3
    0
    0
    1
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    7 / 60 (11.67%)
    8 / 78 (10.26%)
    3 / 24 (12.50%)
    5 / 61 (8.20%)
         occurrences all number
    7
    8
    3
    5
    Nasopharyngitis
         subjects affected / exposed
    4 / 60 (6.67%)
    4 / 78 (5.13%)
    1 / 24 (4.17%)
    4 / 61 (6.56%)
         occurrences all number
    4
    4
    1
    4
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 60 (6.67%)
    3 / 78 (3.85%)
    3 / 24 (12.50%)
    2 / 61 (3.28%)
         occurrences all number
    4
    3
    3
    2
    Cellulitis
         subjects affected / exposed
    3 / 60 (5.00%)
    0 / 78 (0.00%)
    2 / 24 (8.33%)
    0 / 61 (0.00%)
         occurrences all number
    3
    0
    2
    0
    Pneumonia
         subjects affected / exposed
    1 / 60 (1.67%)
    1 / 78 (1.28%)
    2 / 24 (8.33%)
    0 / 61 (0.00%)
         occurrences all number
    1
    1
    2
    0

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Jul 2014
    Amendment 1 included the following key changes: • Increased the total number of subjects planned from 150 to 200 • Increased the number of study sites from approximately 45 to 55 to 80 and broadened the potential regions from the US and Canada to worldwide • Changed the efficacy measure from the Unified Dyskinesia Rating Scale (UDysRS) to the MDS-UPDRS. (Note: A total of 9 subjects provided UDysRS data prior to Amendment 1; all 9 subjects provided data at Screening, and 4 of these subjects provided data at Week 4. The UDysRS data from these subjects are not included in the database and are not discussed in this clinical study report.) • Allowed entry of subjects who had undergone DBS • Broadened entry criteria to allow subjects from any ADS-5102 LID efficacy study, rather than just ADS-AMT-PD301 • Categorized subjects entering the study into 3 groups, for clarity • Removed the need to keep concomitant medications stable while on study • Removed a washout period for prior amantadine use • For subjects in Group 3, removed the exclusion of lack of response to prior amantadine
    07 Oct 2014
    Amendment 2 included the following key changes: • Added US IND number and EudraCT number • Clarified that the end of the study was when the last subject completed the last visit • For subjects in Group 3, modified exclusion criterion regarding cancer from “history of cancer since completion of participation in previous Adamas trial” to “history of cancer within 5 years of Screening” • Added statement that labeling of study drug would be compliant with European Union guidelines • Added that dosing details of an overdose of study drug or a concomitant medication were to be recorded on the appropriate eCRF(s) • Added definition of a suspected unexpected serious adverse reaction • Clarified definition of an unexpected SAE • Updated AE reporting requirements to include Eudravigilance • Updated language regarding subject confidentiality and ethical conduct of the study
    07 Jan 2015
    Amendment 3 included the following key changes: • Revised exclusion criterion regarding sexually active females to specify that a highly effective hormonal method of contraception was to be used in combination with a barrier method (Groups 1, 2, and 3) • Added that subjects with untreated angle closure glaucoma would be excluded (Groups 2 and 3) • Added that subjects with suicidal ideation, history of suicidal ideation, or suicide attempt during prior amantadine use would be excluded (Groups 2 and 3) • Added that subjects were not eligible for study participation if they were taking a medication that could prolong the QT interval and had a known risk of torsades de pointes; to be eligible for the study, the medication had to have been stopped 60 days prior to Screening. Added a list of these types of medications to an appendix • Added a urine pregnancy test at Week 4, 8, 16, 28, 40, and 52
    16 Jul 2015
    Amendment 4 included the following key changes: • Increased the number of subjects (up to 250) and increased the number of study sites (to approximately 90) • Increased the treatment duration to 101 weeks. Added clinical visits and modified procedures and assessments to accommodate this longer treatment duration • Clarified that male or female subjects, 35 to 85 years of age, inclusive, were eligible for study participation (Group 3) • Deleted a reference to use of the mixed model for repeated measures statistical method, which are not appropriate for this open label study. • Clarified that observed data would be reported and that missing data would not be imputed. Note: although this statement was added to the protocol amendment, the statistical analysis plan included imputation rules for missing efficacy data as well as for missing dates of prior medications and AEs, and missing AE causality.

    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.
    For non-serious adverse events only the number of subjects experiencing each event were reported, not number of occurrences. Therefore the number of occurrences is entered as the number of subjects experiencing the event.
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA