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    Clinical Trial Results:
    An open-label extension study to evaluate the long-term safety and tolerability of Idalopirdine (Lu AE58054) as adjunctive treatment to donepezil in patients with mild-moderate Alzheimer's disease

    Summary
    EudraCT number
    		 2013-000001-23
    Trial protocol
    		 CZ   DE   EE   IT   BE   LT   ES   DK   BG   PT   GB   HU   FI   HR  
    Global end of trial date
    06 Jul 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    21 Jul 2018
    First version publication date
    21 Jul 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    14861B STAR EXTENSION
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02079246
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    H. Lundbeck A/S
    Sponsor organisation address
    Ottiliavej 9, Valby, Denmark, 2500
    Public contact
    lundbeckclinicaltrials@lundbeck.com, H- Lundbeck A/S, lundbeckclinicaltrials@lundbeck.com
    Scientific contact
    lundbeckclinicaltrials@lundbeck.com, H- Lundbeck A/S, +45 36301311, lundbeckclinicaltrials@lundbeck.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
    06 Jul 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    06 Jul 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Jul 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Open-label Treatment Period (OLEX): To evaluate the long-term safety and tolerability of idalopirdine as adjunctive therapy to donepezil in patients with mild-moderate AD. Open-label Treatment Period with Memantine (OLEX-MEM): To evaluate the safety and tolerability of concomitant treatment with idalopirdine, memantine and donepezil in patients with AD.
    Protection of trial subjects
    The trial was conducted in accordance with the Declaration of Helsinki (2013) and ICH Good Clinical Practice (1996).
    Background therapy
    		 This is an interventional, multi-national, multi-site, open-label extension study in patients with mild to moderate AD who completed the 24-week lead-in study 14861A (NCT01955161) or 14862A (NCT02006641). Patients received 28-weeks of open-label treatment with idalopirdine 60 mg/day (option to reduce to 30 mg/day) as adjunctive treatment to donepezil. Approximately 100 patients, who had completed the initial 28-week period (OLEX), were included in a 24 week open-label treatment period with memantine (OLEX-MEM) that evaluated the safety and tolerability of concomitant memantine therapy in patients who were already on a stable treatment with idalopirdine and donepezil and for whom memantine treatment was clinically indicated.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    31 Mar 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 139
    Country: Number of subjects enrolled
    Portugal: 12
    Country: Number of subjects enrolled
    Romania: 6
    Country: Number of subjects enrolled
    Spain: 50
    Country: Number of subjects enrolled
    United Kingdom: 66
    Country: Number of subjects enrolled
    Croatia: 11
    Country: Number of subjects enrolled
    Belgium: 13
    Country: Number of subjects enrolled
    Bulgaria: 52
    Country: Number of subjects enrolled
    Czech Republic: 135
    Country: Number of subjects enrolled
    Denmark: 11
    Country: Number of subjects enrolled
    Estonia: 44
    Country: Number of subjects enrolled
    Finland: 13
    Country: Number of subjects enrolled
    France: 71
    Country: Number of subjects enrolled
    Germany: 52
    Country: Number of subjects enrolled
    Hungary: 10
    Country: Number of subjects enrolled
    Italy: 82
    Country: Number of subjects enrolled
    Lithuania: 34
    Country: Number of subjects enrolled
    United States: 236
    Country: Number of subjects enrolled
    Korea, Republic of: 40
    Country: Number of subjects enrolled
    Brazil: 30
    Country: Number of subjects enrolled
    Chile: 79
    Country: Number of subjects enrolled
    Argentina: 119
    Country: Number of subjects enrolled
    Ukraine: 47
    Country: Number of subjects enrolled
    Canada: 51
    Country: Number of subjects enrolled
    Taiwan: 15
    Country: Number of subjects enrolled
    South Africa: 39
    Country: Number of subjects enrolled
    Israel: 5
    Worldwide total number of subjects
    1462
    EEA total number of subjects
    801
    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)
    215
    From 65 to 84 years
    1135
    85 years and over
    112

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Subjects who met each of the inclusion and none of the exclusion criteria were eligible to participate in the study.

    Period 1
    Period 1 title
    OLEX
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Idalopirdine 60 mg
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Idalopirdine 60 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Idalopirdine 60 mg adjunct to 10 mg donepezil. The dose of idalopirdine could be decreased from 60 mg to 30 mg if 60 mg was not well tolerated. The dose of donepezil was to be maintained throughout the study.

    Number of subjects in period 1
    		Idalopirdine 60 mg
    Started
    1462
    Completed
    1235
    Not completed
    227
         Adverse event, serious fatal
    11
         Insufficient compliance
    2
         Withdrawal of caregiver consent
    1
         Worsening of condition
    1
         Results of the lead-in studies
    58
         Moved to nursing home
    1
         Consent withdrawn by subject
    60
         Adverse event, non-fatal
    66
         Caregiver unavailable
    3
         Lost to follow-up
    6
         Disallowed medication
    8
         Protocol deviation
    6
         Lack of efficacy
    3
         Coordinator decision
    1
    Period 2
    Period 2 title
    OLEX-MEM
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Idalopirdine 60 mg + memantine
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Idalopirdine 60 mg + memantine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Idalopirdine 60 mg as adjunct to 10 mg donepezil and memantine (patient's individualised maintenance dose, either immediate-release (IR) 20 mg/day (recommended target dose) or extended release (XR) 28 mg/day (recommended target dose). Memantine was administered to approximately 100 patients included in the OLEX-MEM. The dose of idalopirdine could be decreased from 60 mg to 30 mg if 60 mg was not well tolerated. The dose of donepezil was to be maintained throughout the study. The dose of memantine could be changed at any time throughout the study.

    Number of subjects in period 2 [1]
    		Idalopirdine 60 mg + memantine
    Started
    101
    Completed
    82
    Not completed
    19
         Moved to nursing home
    3
         Consent withdrawn by subject
    7
         Adverse event, non-fatal
    6
         Lost to follow-up
    1
         Protocol deviation
    2
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: 101 patients, who had completed the initial 28-week period (OLEX), were included in a 24 week open-label treatment period with memantine (OLEX-MEM) that evaluated the safety and tolerability of concomitant memantine therapy in patients who were already on a stable treatment with idalopirdine and donepezil and for whom memantine treatment was clinically indicated.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    OLEX
    Reporting group description
    		 -

    Reporting group values
    		 OLEX Total
    Number of subjects
    		 1462 1462
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 73.7 ± 8.2 -
    Gender categorical
    Units: Subjects
        Female
    		 922 922
        Male
    		 540 540
    Race
    Units: Subjects
        Asian
    		 63 63
        Black or African American
    		 17 17
        White
    		 1318 1318
        Unknown or Not Reported
    		 62 62
        NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER
    		 2 2

    End points

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    End points reporting groups
    Reporting group title
    Idalopirdine 60 mg
    Reporting group description
    		 -
    Reporting group title
    Idalopirdine 60 mg + memantine
    Reporting group description
    		 -

    Subject analysis set title
    Idalopirdin 60 mg (OLEX): patients from lead-in study 14861A
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Idalopirdin 60 mg (OLEX): patients from lead-in study 14861

    Subject analysis set title
    Idalopirdin 60 mg (OLEX): patients from lead-in study 14862A
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Idalopirdin 60 mg (OLEX): patients from lead-in study 14862A

    Primary: Number of Treatment Emergent Adverse Events (TEAEs) in the OLEX

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    End point title
    		 Number of Treatment Emergent Adverse Events (TEAEs) in the OLEX [1]
    End point description
    A TEAE is an adverse event that starts or increases in intensity after the date of Baseline II (start of OLEX)
    End point type
    Primary
    End point timeframe
    Baseline II (start of OLEX) to end of OLEX (week 28)
    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: No statistical analysis for this endpoint
    End point values
    		 Idalopirdine 60 mg
    Number of subjects analysed
    1462
    Units: number of TEAEs
    2130
    No statistical analyses for this end point

    Primary: Number of TEAEs in the OLEX-MEM

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    End point title
    		 Number of TEAEs in the OLEX-MEM [2]
    End point description
    A TEAE is an adverse event that starts or increased in intensity after the date of Baseline III (start of OLEX-MEM)
    End point type
    Primary
    End point timeframe
    From Baseline III (start of OLEX-MEM) to end of OLEX-MEM (Week 52)
    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: No statistical analysis for this endpoint
    End point values
    Number of subjects analysed
    Units: Number of TEAEs
    No statistical analyses for this end point

    Secondary: Change in Cognition

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    End point title
    		 Change in Cognition
    End point description
    Change from Baseline II to Week 28 in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) total score. The ADAS-cog is a 11-item neuropsychological test that assess the severity of cognitive impairment. The items determine the patient's orientation, memory, language, and praxis. Total score of the 11 items range from 0 to 70 (lower score indicates lower cognitive impairment).
    End point type
    Secondary
    End point timeframe
    Baseline II (start of OLEX) to Week 28
    End point values
    		 Idalopirdin 60 mg (OLEX): patients from lead-in study 14861A Idalopirdin 60 mg (OLEX): patients from lead-in study 14862A
    Number of subjects analysed
    693
    602
    Units: Units on a scale
        arithmetic mean (standard error)
    3.01 ± 0.22
    2.67 ± 0.23
    No statistical analyses for this end point

    Secondary: Clinical Global Impression Score

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    End point title
    		 Clinical Global Impression Score
    End point description
    Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) score at Week 28. The ADCS-CGIC is a semi-structured interview to assess clinically relevant changes in patients with AD. The items determine cognition, behavior, social and daily functioning. Severity at baseline is rated on a 7-point scale from 1 (normal, not ill at all) to 7 (among the most extremely ill patients). The clinically relevant change from baseline is rated on a 7-point scale from 1 (marked improvement) to 7 (marked worsening).
    End point type
    Secondary
    End point timeframe
    Week 28
    End point values
    		 Idalopirdin 60 mg (OLEX): patients from lead-in study 14861A Idalopirdin 60 mg (OLEX): patients from lead-in study 14862A
    Number of subjects analysed
    693
    594
    Units: units on a scale
        arithmetic mean (standard error)
    4.58 ± 0.005
    4.61 ± 0.05
    No statistical analyses for this end point

    Secondary: Change in Daily Functioning

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    End point title
    		 Change in Daily Functioning
    End point description
    Change from Baseline II to Week 28 in Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL23) total score. The ADCS-ADL23 is a 23-item clinician-rated inventory to assess activities of daily living (conducted with a caregiver or informant). Each item comprises a series of hierarchical sub-questions, ranging from the highest level of independent performance to a complete loss for each activity. Total score of the 23 items ranges from 0 to 78 (higher score indicates lower disability).
    End point type
    Secondary
    End point timeframe
    Baseline II (start of OLEX) to Week 28
    End point values
    		 Idalopirdin 60 mg (OLEX): patients from lead-in study 14861A Idalopirdin 60 mg (OLEX): patients from lead-in study 14862A
    Number of subjects analysed
    Units: units on a scale
        arithmetic mean (standard error)
    -3.71 ± 0.28
    -3.88 ± 0.32
    No statistical analyses for this end point

    Secondary: Change in Behavioural Disturbance

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    End point title
    		 Change in Behavioural Disturbance
    End point description
    Change from Baseline II to Week 28 in Neuropsychiatric Inventory (NPI) total score. The NPI is a 12-item structured interview with a caregiver to assess behavioural disturbances. The NPI comprises 10 behavioural and 2 neurovegetative items. Each item consists of a screening question and several sub-questions that are rated no (not present) or yes (present). Each item is rated for frequency (a 4-point scale from 1 [occasionally] to 4 [very frequent]) and severity (a 3-point scale from 1 [mild] to 3 [marked]). The total NPI score is the frequency ratings multiplied by the severity ratings and ranges from 0 to 144 (higher score indicates worse outcome).
    End point type
    Secondary
    End point timeframe
    Baseline II (start of OLEX) to Week 28
    End point values
    		 Idalopirdin 60 mg (OLEX): patients from lead-in study 14861A Idalopirdin 60 mg (OLEX): patients from lead-in study 14862A
    Number of subjects analysed
    697
    602
    Units: units on a scale
        arithmetic mean (standard error)
    1.80 ± 0.35
    1.36 ± 0.34
    No statistical analyses for this end point

    Secondary: Change in Cognitive Aspects of Mental Function

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    End point title
    		 Change in Cognitive Aspects of Mental Function
    End point description
    Change from Baseline II to Week 28 in Mini Mental State Examination (MMSE). The MMSE is an 11-item test to assess the cognitive aspects of mental function. The subtests assess orientation, memory, attention, language, and visual construction. The scores for each item is dichotomous (1 = response is correct, 0 = response is incorrect). Total score of the 11 items ranges from 0 to 30 (higher score indicates lower deficit).
    End point type
    Secondary
    End point timeframe
    Baseline II (start of OLEX) to Week 28
    End point values
    		 Idalopirdin 60 mg (OLEX): patients from lead-in study 14861A Idalopirdin 60 mg (OLEX): patients from lead-in study 14862A
    Number of subjects analysed
    730
    646
    Units: units on a scale
        arithmetic mean (standard error)
    -1.28 ± 0.10
    -1.02 ± 0.11
    No statistical analyses for this end point

    Secondary: Change in Cognitive Aspects of Mental Function

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    End point title
    		 Change in Cognitive Aspects of Mental Function
    End point description
    Change from Baseline III to Week 52 in Mini Mental State Examination (MMSE). The MMSE is an 11-item test to assess the cognitive aspects of mental function. The subtests assess orientation, memory, attention, language, and visual construction. The scores for each item is dichotomous (1 = response is correct, 0 = response is incorrect). Total score of the 11 items ranges from 0 to 30 (higher score indicates lower deficit).
    End point type
    Secondary
    End point timeframe
    Baseline III (start of OLEX-MEM) to Week 52
    End point values
    Number of subjects analysed
    Units: units on a scale
        arithmetic mean (standard error)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    First dose to follow-up
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Idalopirdine 60 mg
    Reporting group description
    		 Idalopirdine 60 mg

    Reporting group title
    Idalopirdine 60 mg + Memantine
    Reporting group description
    		 Idalopirdine 60 mg + Memantine

    Serious adverse events
    		 Idalopirdine 60 mg Idalopirdine 60 mg + Memantine
    Total subjects affected by serious adverse events
         subjects affected / exposed
    91 / 1462 (6.22%)
    2 / 101 (1.98%)
         number of deaths (all causes)
    11
    0
         number of deaths resulting from adverse events
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign neoplasm
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Benign neoplasm of cervix uteri
         subjects affected / exposed [1]
    1 / 922 (0.11%)
    0 / 69 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Cataract operation
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Exercise tolerance decreased
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Social circumstances
    Social stay hospitalisation
         subjects affected / exposed
    0 / 1462 (0.00%)
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed [2]
    1 / 540 (0.19%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast mass
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Laryngeal haemorrhage
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Abnormal behaviour
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aggression
         subjects affected / exposed
    2 / 1462 (0.14%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Agitation
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    2 / 1462 (0.14%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Delusion
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depressive symptom
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Grief reaction
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    2 / 1462 (0.14%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sleep disorder
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device malfunction
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood potassium decreased
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain contusion
         subjects affected / exposed
    2 / 1462 (0.14%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    6 / 1462 (0.41%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    2 / 1462 (0.14%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    2 / 1462 (0.14%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial tachycardia
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Balance disorder
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain stem infarction
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dementia
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Dementia alzheimer's type
         subjects affected / exposed
    2 / 1462 (0.14%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial haematoma
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    2 / 1462 (0.14%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    2 / 1462 (0.14%)
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Partial seizures
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychomotor hyperactivity
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vertebrobasilar insufficiency
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iris adhesions
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinopathy proliferative
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Calculus urinary
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    2 / 1462 (0.14%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal bacterial infection
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis e
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection bacterial
         subjects affected / exposed
    2 / 1462 (0.14%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection viral
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 1462 (0.21%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    4 / 1462 (0.27%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    2 / 1462 (0.14%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    1 / 1462 (0.07%)
    0 / 101 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This Serious Adverse Event is only applicable for female subjects.
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This Serious Adverse Event is only applicable for male subjects.
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Idalopirdine 60 mg Idalopirdine 60 mg + Memantine
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    182 / 1462 (12.45%)
    7 / 101 (6.93%)
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    105 / 1462 (7.18%)
    6 / 101 (5.94%)
         occurrences all number
    233
    11
    Fall
         subjects affected / exposed
    80 / 1462 (5.47%)
    1 / 101 (0.99%)
         occurrences all number
    93
    1

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Feb 2014
    Protocol Amendment PA01: The main reason for this amendment is the decision that only patients from lead-in studies 14861A and 14862A will enter into the extension study 14861B. Further, changes of eligibility criteria and clarifications where needed.
    16 Jun 2015
    Protocol Amendment CSPA02: for Bulgaria, Canada, Czech Republic, Estonia, Germany, France, Italy, Lithuania, Poland, South Korea, Spain, United Kingdom and United States. AD is a progressive neurodegenerative disease that is characterised by a steady decline in a patient’s cognition and function and an increase in behavioural problems. Thus in a complex disease like AD, there is a strong medical need for alternative treatment options which include combining the different symptomatic treatments with diverse pharmacological modes of action. The open-label treatment period with memantine (substudy) will evaluate the safety and tolerability of adding memantine therapy in patients who are already on a stable treatment of idalopirdine and donepezil and for whom memantine treatment is clinically indicated. Concomitant treatment with the three compounds has not been studied in previous or ongoing clinical trials. Furthermore, adjunctive treatment with memantine is likely to be a common treatment option for patients with AD soon after idalopirdine becomes available. Thus the open-label treatment period with memantine (substudy) is designed to inform potential future clinicians and patients of the safety and tolerability profile to expect when idalopirdine, memantine and donepezil are taken concomitantly.

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

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