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   43851   clinical trials with a EudraCT protocol, of which   7283   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:
    A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Investigate the Efficacy and Safety of RO4995819 Versus Placebo, as Adjunctive Therapy in Patients with Major Depressive Disorder Having Inadequate Response to Ongoing Antidepressant Treatment

    Summary
    EudraCT number
    		 2011-002160-24
    Trial protocol
    		 AT   DE   SK  
    Global end of trial date
    04 Jun 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 Jul 2016
    First version publication date
    17 Jul 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    BP25712
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01457677
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche Ltd
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, 4070
    Public contact
    Trial Information Support Line-TISL, F.Hoffmann-La Roche Ltd., +41 61688 1111, global.rochegenentechtrials@roche.com
    Scientific contact
    Trial Information Support Line-TISL, F.Hoffmann-La Roche Ltd., +41 61688 1111, global.rochegenentechtrials@roche.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
    17 Jul 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Jun 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of 6 weeks treatment of RO4995819 versus placebo as adjunctive therapy in patients with MDD having inadequate response to ongoing antidepressant treatment based on mean change in Montgomery Asberg Depression Rating Scale (MADRS) scores from baseline to end of treatment.
    Protection of trial subjects
    Participants were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. The participants were provided an Emergency Medical Call Center Help Desk in the case of emergency during the study to ensure the safety . An Independent Data Monitoring Committee (IDMC) supervised the participants safety.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    03 Oct 2011
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 2 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Slovakia: 12
    Country: Number of subjects enrolled
    Austria: 4
    Country: Number of subjects enrolled
    Germany: 26
    Country: Number of subjects enrolled
    Canada: 26
    Country: Number of subjects enrolled
    Russian Federation: 50
    Country: Number of subjects enrolled
    South Africa: 14
    Country: Number of subjects enrolled
    Ukraine: 34
    Country: Number of subjects enrolled
    United States: 191
    Worldwide total number of subjects
    357
    EEA total number of subjects
    42
    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)
    353
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This study was conducted from 01 December 2011 to 04 June 2014 in 72 sites in 8 countries. The 30 mg RO4995819 arm was dropped after the interim analysis, and therefore contains a smaller number of patients compared with the other arms.

    Pre-assignment
    Screening details
    		 A total of 357 patients were enrolled in the study.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received placebo oral once daily for 6 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were to take matching placebo capsule orally once daily for 6 weeks.

    Arm title
    		 RO4995819 5mg
    Arm description
    		 Participants received RO4995819 5 mg oral once daily for 6 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    RO4995819
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were to take RO4995819 5 mg capsule orally once daily for 6 weeks.

    Arm title
    		 RO4995819 15mg
    Arm description
    		 Participants received RO4995819 15 mg oral once daily for 6 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    RO4995819
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were to take RO4995819 15 mg capsule orally once daily for 6 weeks.

    Arm title
    		 RO4995819 30mg
    Arm description
    		 Participants received RO4995819 30 mg oral once daily for 6 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    RO4995819
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were to take RO4995819 30 mg capsule orally once daily for 6 weeks.

    Number of subjects in period 1
    		Placebo RO4995819 5mg RO4995819 15mg RO4995819 30mg
    Started
    99
    101
    102
    55
    Completed
    87
    85
    84
    45
    Not completed
    12
    16
    18
    10
         Consent withdrawn by subject
    2
    8
    7
    1
         Failure to return
    3
    1
    3
    3
         Adverse event, non-fatal
    1
    5
    4
    5
         Violation of selection criteria at entry
    1
    -
    1
    1
         Administrative/Other
    4
    2
    3
    -
         Refused Treatment/Did Not Cooperate
    1
    -
    -
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo oral once daily for 6 weeks.

    Reporting group title
    RO4995819 5mg
    Reporting group description
    		 Participants received RO4995819 5 mg oral once daily for 6 weeks.

    Reporting group title
    RO4995819 15mg
    Reporting group description
    		 Participants received RO4995819 15 mg oral once daily for 6 weeks.

    Reporting group title
    RO4995819 30mg
    Reporting group description
    		 Participants received RO4995819 30 mg oral once daily for 6 weeks.

    Reporting group values
    		 Placebo RO4995819 5mg RO4995819 15mg RO4995819 30mg Total
    Number of subjects
    		 99 101 102 55 357
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 45.7 ± 11.3 46.1 ± 11.2 46.3 ± 11.5 44.6 ± 12.9 -
    Gender categorical
    Units: Subjects
        Female
    		 69 71 69 38 247
        Male
    		 30 30 33 17 110

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo oral once daily for 6 weeks.

    Reporting group title
    RO4995819 5mg
    Reporting group description
    		 Participants received RO4995819 5 mg oral once daily for 6 weeks.

    Reporting group title
    RO4995819 15mg
    Reporting group description
    		 Participants received RO4995819 15 mg oral once daily for 6 weeks.

    Reporting group title
    RO4995819 30mg
    Reporting group description
    		 Participants received RO4995819 30 mg oral once daily for 6 weeks.

    Subject analysis set title
    Per protocol
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Per protocol population included all participants who were randomized, had a valid baseline assessment of the MADRS total score (centralized rating) and at “Day 42/Early Withdrawal” Visit.

    Subject analysis set title
    Safety population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The safety population consisted of all participants who have received at least one dose of study medication and had at least one post-dose safety assessment, whether withdrawn prematurely or not.

    Primary: Mean Change from Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score at Day 42

    		 Close Top of page
    End point title
    		 Mean Change from Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score at Day 42
    End point description
    The MADRS is a 10-item scale designed to measure depression severity and detects changes due to antidepressant treatment. Each item is scored on a 7-point scale and the scores range from "0 = item not present or normal" to "6 = severe or continuous presence of the symptoms". Total score is calculated by adding the scores for all the 10 items and it will range from "0 to 60". The interpretation of the scores are: 0 to 6 – normal/symptom absent; 7 to 19 – mild depression; 20 to 34 – moderate depression; > 34 – severe depression. Higher scores represent a more severe condition. Per protocol population was used for this analysis.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1) and Day 42
    End point values
    		 Placebo RO4995819 5mg RO4995819 15mg RO4995819 30mg
    Number of subjects analysed
    86 [1]
    89 [2]
    88 [3]
    47 [4]
    Units: Units on scale
        least squares mean (confidence interval 95%)
    -11.77 (-14.16 to -9.38)
    -12.82 (-15.18 to -10.46)
    -11.79 (-14.16 to -9.42)
    -13.2 (-16.42 to -9.99)
    Notes
    [1] - Only those participants available at the specified time points were analyzed
    [2] - Only those participants available at the specified time points were analyzed
    [3] - Only those participants available at the specified time points were analyzed
    [4] - Only those participants available at the specified time points were analyzed
    Statistical analysis title
    		 Effect of 05 mg dose Vs Placebo
    Comparison groups
    Placebo v RO4995819 5mg
    Number of subjects included in analysis
    175
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.53
    Method
    		 Mixed models analysis
    Parameter type
    		 Effect
    Point estimate
    -1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.36
         upper limit
    		 2.26
    Statistical analysis title
    		 Effect of 15 mg dose Vs Placebo
    Comparison groups
    Placebo v RO4995819 15mg
    Number of subjects included in analysis
    174
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.99
    Method
    		 Mixed models analysis
    Parameter type
    		 Effect
    Point estimate
    -1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.34
         upper limit
    		 3.3
    Statistical analysis title
    		 Copy of Effect of 30 mg dose Vs Placebo
    Comparison groups
    RO4995819 30mg v Placebo
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.48
    Method
    		 Mixed models analysis
    Parameter type
    		 Effect
    Point estimate
    -1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.41
         upper limit
    		 2.54

    Secondary: Number of Participants with Adverse Events

    		 Close Top of page
    End point title
    		 Number of Participants with Adverse Events
    End point description
    An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Safety population was used for this analysis.
    End point type
    Secondary
    End point timeframe
    Up to Day 98
    End point values
    		 Placebo RO4995819 5mg RO4995819 15mg RO4995819 30mg
    Number of subjects analysed
    99
    101
    102
    55
    Units: Participants
        Participants with AEs
    74
    76
    79
    47
        Serious Adverse Events
    1
    3
    2
    0
        AE leading to withdrawal
    1
    4
    4
    5
    No statistical analyses for this end point

    Secondary: Number of Participants Exhibiting Remission (a MADRS score of <=10)

    		 Close Top of page
    End point title
    		 Number of Participants Exhibiting Remission (a MADRS score of <=10)
    End point description
    Number of participants in remission with one previous treatment failure and with total Montgomery Asberg Depression Rating Scale (MADRS) score <=10. The MADRS is a 10-item scale designed to measure depression severity and detects changes due to antidepressant treatment. Each item is scored on a 7-point scale and the scores range from "0 = item not present or normal" to "6 = severe or continuous presence of the symptoms". Total score is calculated by adding the scores for all the 10 items and it will range from "0 to 60". The interpretation of the scores are: 0 to 6 – normal/symptom absent; 7 to 19 – mild depression; 20 to 34 – moderate depression; > 34 – severe depression. Higher scores represent a more severe condition. Per protocol population was used for this analysis.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Day 42
    End point values
    		 Placebo RO4995819 5mg RO4995819 15mg RO4995819 30mg
    Number of subjects analysed
    86
    89
    88
    47
    Units: Participants
    25
    31
    25
    13
    No statistical analyses for this end point

    Secondary: Number of Participants Exhibiting Response (reduction in MADRS score of >= 50% of the baseline score)

    		 Close Top of page
    End point title
    		 Number of Participants Exhibiting Response (reduction in MADRS score of >= 50% of the baseline score)
    End point description
    Number of participants with reduction of >=50 percent (%) in MADRS total score (indicates response). The MADRS is a 10-item scale designed to measure depression severity and detects changes due to antidepressant treatment. Each item is scored on a 7-point scale and the scores range from "0 = item not present or normal" to "6 = severe or continuous presence of the symptoms". Total score is calculated by adding the scores for all the 10 items and it will range from "0 to 60". The interpretation of the scores are: 0 to 6 – normal/symptom absent; 7 to 19 – mild depression; 20 to 34 – moderate depression; > 34 – severe depression. Higher scores represent a more severe condition. Per protocol population was used for this analysis.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Day 42
    End point values
    		 Placebo RO4995819 5mg RO4995819 15mg RO4995819 30mg
    Number of subjects analysed
    86
    89
    88
    47
    Units: Participants
    29
    32
    33
    18
    No statistical analyses for this end point

    Secondary: Number of Participants with Abnormalities in Neurological Examination

    		 Close Top of page
    End point title
    		 Number of Participants with Abnormalities in Neurological Examination
    End point description
    Number of participants with abnormalities in neurological examinations as determined by the investigators. Neurological examinations included assessment of general tone, power, sensation, deep reflexes, gait, balance, coordination, ocular movements and mental status. Safety population was used for this analysis.
    End point type
    Secondary
    End point timeframe
    Up to 14 weeks
    End point values
    		 Placebo RO4995819 5mg RO4995819 15mg RO4995819 30mg
    Number of subjects analysed
    99
    101
    102
    55
    Units: Participants
    2
    3
    4
    0
    No statistical analyses for this end point

    Secondary: Change from Baseline in Extrapyramidal Symptom Rating Scale (Abbreviated)

    		 Close Top of page
    End point title
    		 Change from Baseline in Extrapyramidal Symptom Rating Scale (Abbreviated)
    End point description
    The ESRS is a 12-item clinician-rated scale designed to assess the severity of extrapyramidal symptoms. Dyskinesic movements are rated according to both frequency and amplitude. It measures the four types of drug-induced movement disorders (Parkinsonism, Dystonia, akathisia, and Dyskinesia). Items are rated on a "6 point scale ranging from 0 (normal) to 5 (extremely severe)". The higher the score, the more severely the symptoms affect function. Safety population was used for this analysis.
    End point type
    Secondary
    End point timeframe
    Up to 14 weeks
    End point values
    		 Placebo RO4995819 5mg RO4995819 15mg RO4995819 30mg
    Number of subjects analysed
    90
    90
    88
    49
    Units: Units on a scale
        arithmetic mean (standard deviation)
    -0.08 ± 0.46
    -0.1 ± 0.45
    -0.09 ± 0.4
    -0.02 ± 0.16
    No statistical analyses for this end point

    Secondary: Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)

    		 Close Top of page
    End point title
    		 Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)
    End point description
    The C-SSRS is a tool used to assess the lifetime suicidality of a patient (C-SSRS screening/baseline) as well as any new instances of suicidality (C-SSRS since last visit). The CSSRS incorporates a structured interview to prompt recollection of suicidal ideation, including the intensity of the ideation, behavior and attempts with actual/potential lethality. Safety population was used for this analysis.
    End point type
    Secondary
    End point timeframe
    Baseline to 14 Weeks
    End point values
    		 Placebo RO4995819 5mg RO4995819 15mg RO4995819 30mg
    Number of subjects analysed
    99
    101
    102
    55
    Units: Participants
        Suicidal Ideation
    23
    18
    22
    12
        Suicidal Behavior
    0
    1
    1
    0
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    14 weeks
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Patients who received placebo oral once daily for 6 weeks

    Reporting group title
    RO4995819 5mg
    Reporting group description
    		 Particpants who received RO4995819 5 mg oral once daily for 6 weeks.

    Reporting group title
    RO4995819 15mg
    Reporting group description
    		 Particpants who received RO4995819 15 mg oral once daily for 6 weeks.

    Reporting group title
    RO4995819 30mg
    Reporting group description
    		 Particpants who received RO4995819 30 mg oral once daily for 6 weeks.

    Serious adverse events
    		 Placebo RO4995819 5mg RO4995819 15mg RO4995819 30mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 99 (1.01%)
    3 / 101 (2.97%)
    2 / 102 (1.96%)
    0 / 55 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Social circumstances
    Pregnancy of partner
         subjects affected / exposed
    0 / 99 (0.00%)
    0 / 101 (0.00%)
    1 / 102 (0.98%)
    0 / 55 (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
    Gastrointestinal disorders
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 99 (1.01%)
    0 / 101 (0.00%)
    0 / 102 (0.00%)
    0 / 55 (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
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 99 (0.00%)
    1 / 101 (0.99%)
    0 / 102 (0.00%)
    0 / 55 (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
    Suicidal ideation
         subjects affected / exposed
    0 / 99 (0.00%)
    0 / 101 (0.00%)
    1 / 102 (0.98%)
    0 / 55 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 99 (0.00%)
    1 / 101 (0.99%)
    0 / 102 (0.00%)
    0 / 55 (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
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 99 (0.00%)
    1 / 101 (0.99%)
    0 / 102 (0.00%)
    0 / 55 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo RO4995819 5mg RO4995819 15mg RO4995819 30mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    74 / 99 (74.75%)
    76 / 101 (75.25%)
    79 / 102 (77.45%)
    47 / 55 (85.45%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    27 / 99 (27.27%)
    22 / 101 (21.78%)
    31 / 102 (30.39%)
    16 / 55 (29.09%)
         occurrences all number
    48
    70
    85
    27
    Dizziness
         subjects affected / exposed
    12 / 99 (12.12%)
    12 / 101 (11.88%)
    21 / 102 (20.59%)
    22 / 55 (40.00%)
         occurrences all number
    20
    17
    32
    54
    Somnolence
         subjects affected / exposed
    1 / 99 (1.01%)
    7 / 101 (6.93%)
    4 / 102 (3.92%)
    2 / 55 (3.64%)
         occurrences all number
    1
    8
    4
    2
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    3 / 99 (3.03%)
    4 / 101 (3.96%)
    4 / 102 (3.92%)
    4 / 55 (7.27%)
         occurrences all number
    4
    4
    5
    5
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    15 / 99 (15.15%)
    10 / 101 (9.90%)
    25 / 102 (24.51%)
    17 / 55 (30.91%)
         occurrences all number
    19
    14
    32
    27
    Diarrhoea
         subjects affected / exposed
    10 / 99 (10.10%)
    11 / 101 (10.89%)
    6 / 102 (5.88%)
    7 / 55 (12.73%)
         occurrences all number
    18
    17
    7
    10
    Vomiting
         subjects affected / exposed
    5 / 99 (5.05%)
    6 / 101 (5.94%)
    10 / 102 (9.80%)
    10 / 55 (18.18%)
         occurrences all number
    6
    9
    12
    31
    Abdominal pain upper
         subjects affected / exposed
    6 / 99 (6.06%)
    1 / 101 (0.99%)
    1 / 102 (0.98%)
    2 / 55 (3.64%)
         occurrences all number
    13
    1
    2
    3
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    6 / 99 (6.06%)
    10 / 101 (9.90%)
    8 / 102 (7.84%)
    2 / 55 (3.64%)
         occurrences all number
    8
    12
    10
    2
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 99 (1.01%)
    2 / 101 (1.98%)
    5 / 102 (4.90%)
    6 / 55 (10.91%)
         occurrences all number
    1
    2
    6
    6
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    7 / 99 (7.07%)
    3 / 101 (2.97%)
    10 / 102 (9.80%)
    4 / 55 (7.27%)
         occurrences all number
    7
    3
    12
    4
    Upper respiratory tract infection
         subjects affected / exposed
    7 / 99 (7.07%)
    7 / 101 (6.93%)
    4 / 102 (3.92%)
    1 / 55 (1.82%)
         occurrences all number
    8
    8
    4
    1
    Influenza
         subjects affected / exposed
    4 / 99 (4.04%)
    6 / 101 (5.94%)
    4 / 102 (3.92%)
    3 / 55 (5.45%)
         occurrences all number
    4
    6
    4
    3
    Ear infection
         subjects affected / exposed
    0 / 99 (0.00%)
    1 / 101 (0.99%)
    0 / 102 (0.00%)
    3 / 55 (5.45%)
         occurrences all number
    0
    1
    0
    3

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Sep 2011
    Modifications to inclusion criteria re outpatient status & medications. Removal of AESIs. Modification of PK sampling.
    28 Nov 2011
    Addition of neurological & cognitive examinations. Removal of 'recurrent' from diagnostic criteria.
    26 Jan 2012
    Addition of updated toxicological Data. CZ country-specific change upper limit on the CGI-S.
    10 May 2012
    Clarification of suicidal risk assessment, change in version of CSSRS used at screening. Modification of prohibited medications. Addition of pepsinogen test, cotinine test. Update to SAE/pregnancy reporting. Consent requirement for pregnant partner. Additional potential exploratory post-hoc analyses. Admin changes (# study centres, clarifications, correction of typographical errors).
    28 Nov 2012
    Change to D1 post-dose monitoring and ePK schedule. Change to sample size & interim analysis. Inclusion of re-screening (for non-medical fails) and extension of screening period.

    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-Sat Apr 20 18:16:46 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA