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    Clinical Trial Results:
    Assessment of Safety, Tolerability, and Pharmacodynamic Effects of LY2886721 in Patients with Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease

    Summary
    EudraCT number
    		 2011-005217-37
    Trial protocol
    		 NL   ES   IT  
    Global end of trial date
    06 Aug 2013

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Apr 2018
    First version publication date
    09 Apr 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    I4O-MC-BACC
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01561430
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon - Fri 9 AM - 5 PM EST, Eli Lilly and Company, 1 877-285-4559,
    Scientific contact
    Available Mon - Fri 9 AM - 5 PM EST, Eli Lilly and Company, 1 877-CTLILLY,
    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 Aug 2013
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Aug 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this Phase 1/Phase 2 study is to evaluate how the body handles the drug and the drug's effect on the body of participants with mild cognitive impairment (MCI) due to Alzheimer's Disease (AD) or mild AD and who test positive for amyloid plaque.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    22 Mar 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 60
    Country: Number of subjects enrolled
    Netherlands: 5
    Country: Number of subjects enrolled
    Japan: 5
    Worldwide total number of subjects
    70
    EEA total number of subjects
    5
    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)
    28
    From 65 to 84 years
    39
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 As a result of findings from the I4O-MC-BACJ study (NCT01534273), enrollment was discontinued to the 15 milligrams (mg) arm. The 9 participants already enrolled were allowed to continue study treatment at the 15 mg dose.

    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, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 15 mg LY2886721
    Arm description
    		 LY2886721: 15 milligrams (mg), capsules, administered orally, once daily for 26 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    15 mg LY2886721
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    LY2886721: 15 milligrams (mg), capsules, administered orally, once daily for 26 weeks.

    Arm title
    		 35 mg LY2886721
    Arm description
    		 LY2886721: 35 mg, capsules, administered orally, once daily for 26 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    35 mg LY2886721
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    LY2886721: 35 mg, capsules, administered orally, once daily for 26 weeks.

    Arm title
    		 70 mg LY2886721
    Arm description
    		 LY2886721: 70 mg, capsules, administered orally, once daily for 26 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    70 mg LY2886721
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    LY2886721: 70 mg, capsules, administered orally, once daily for 26 weeks.

    Arm title
    		 Placebo
    Arm description
    		 Placebo: 1 placebo capsule, administered orally, once daily for 26 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
    Placebo: 1 placebo capsule, administered orally, once daily for 26 weeks.

    Number of subjects in period 1
    		15 mg LY2886721 35 mg LY2886721 70 mg LY2886721 Placebo
    Started
    9
    23
    18
    20
    Received at Least One Dose of Study Drug
    9
    23
    18
    20
    Completed
    8
    8
    1
    7
    Not completed
    1
    15
    17
    13
         Physician decision
    -
    1
    -
    -
         Consent withdrawn by subject
    -
    -
    1
    -
         Adverse event, non-fatal
    -
    -
    3
    1
         Sponsor Decision
    1
    14
    13
    12

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall Study
    Reporting group description
    		 -

    Reporting group values
    		 Overall Study Total
    Number of subjects
    		 70 70
    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)
    		 28 28
        From 65-84 years
    		 39 39
        85 years and over
    		 3 3
    Gender, Male/Female
    Units:
        Female
    		 33 33
        Male
    		 37 37
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    		 0 0
        Asian
    		 6 6
        Black or African American
    		 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0
        White
    		 64 64
    Region of Enrollment
    Units: Subjects
        United States
    		 60 60
        Netherlands
    		 5 5
        Japan
    		 5 5

    End points

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    End points reporting groups
    Reporting group title
    15 mg LY2886721
    Reporting group description
    		 LY2886721: 15 milligrams (mg), capsules, administered orally, once daily for 26 weeks.

    Reporting group title
    35 mg LY2886721
    Reporting group description
    		 LY2886721: 35 mg, capsules, administered orally, once daily for 26 weeks.

    Reporting group title
    70 mg LY2886721
    Reporting group description
    		 LY2886721: 70 mg, capsules, administered orally, once daily for 26 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo: 1 placebo capsule, administered orally, once daily for 26 weeks.

    Primary: Change from Baseline to 12 Weeks in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations

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    End point title
    		 Change from Baseline to 12 Weeks in Cerebrospinal Fluid (CSF) Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations
    End point description
    Percent change in lumbar CSF concentrations of Aβ1-40 and Aβ1-42 from baseline at 12 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL). Least Squares (LS) means of percent change in concentration from baseline was calculated using analysis of covariance (ANCOVA) with baseline as a covariate and treatment as a fixed effect. Analysis Population Description: All randomized participants with evaluable post-baseline CSF Aβ1-40 or Aβ1-42 data.
    End point type
    Primary
    End point timeframe
    Baseline, 12 weeks
    End point values
    		 15 mg LY2886721 35 mg LY2886721 70 mg LY2886721 Placebo
    Number of subjects analysed
    7
    9
    5
    12
    Units: percent change in Aβ1-40 and Aβ1-42
    least squares mean (standard error)
        Aβ1-40 (n=7, 9, 5, 11)
    -31.8 ± 7.35
    -57.7 ± 6.67
    -58.9 ± 8.73
    3.7 ± 5.96
        Aβ1-42 (n=7, 9, 5, 12)
    -34.4 ± 7.27
    -52 ± 6.8
    -60.7 ± 8.42
    6.5 ± 6.06
    Statistical analysis title
    		 15 mg Change from Baseline to Week 12 CSF Aβ1-40
    Comparison groups
    15 mg LY2886721 v Placebo
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Least Squares Mean
    Point estimate
    -31.8
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -41.4
         upper limit
    		 -22.1
    Variability estimate
    Standard error of the mean
    Statistical analysis title
    		 35 mg Change from Baseline to Week 12 CSF Aβ1-40
    Comparison groups
    35 mg LY2886721 v Placebo
    Number of subjects included in analysis
    21
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Least Squre Means
    Point estimate
    -57.7
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -66.4
         upper limit
    		 -48.9
    Variability estimate
    Standard error of the mean
    Statistical analysis title
    		 70 mg Change from Baseline to Week 12 CSF Aβ1-40
    Comparison groups
    70 mg LY2886721 v Placebo
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Least Squares Mean
    Point estimate
    -58.9
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -70.4
         upper limit
    		 -47.4
    Variability estimate
    Standard error of the mean
    Statistical analysis title
    		 15mg Change from Baseline to 12 Weeks CSF Aβ1-42
    Comparison groups
    Placebo v 15 mg LY2886721
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Least Squares Mean
    Point estimate
    -34.4
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -44
         upper limit
    		 -24.9
    Variability estimate
    Standard error of the mean
    Statistical analysis title
    		 35 mg Change from Baseline to 12 Weeks CSF Aβ1-42
    Comparison groups
    35 mg LY2886721 v Placebo
    Number of subjects included in analysis
    21
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Least Squares Mean
    Point estimate
    -52
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -60.9
         upper limit
    		 -43.1
    Variability estimate
    Standard error of the mean
    Statistical analysis title
    		 70 mg Change from Baseline to 12 Weeks CSF Aβ1-42
    Comparison groups
    70 mg LY2886721 v Placebo
    Number of subjects included in analysis
    17
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Least Squares Mean
    Point estimate
    -60.7
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -71.7
         upper limit
    		 -49.6
    Variability estimate
    Standard error of the mean

    Primary: Change from Baseline to 26 Weeks in CSF Aβ1-40 and Aβ1-42 Concentrations

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    End point title
    		 Change from Baseline to 26 Weeks in CSF Aβ1-40 and Aβ1-42 Concentrations [1]
    End point description
    Percent change in lumbar CSF concentrations of Aβ1-40 and Aβ1-42 from baseline at 26 weeks post-dose was to be calculated. The units for CSF were picograms per milliliter (pg/mL). LS means of percent change in concentration from baseline was calculated using ANCOVA with baseline as a covariate and treatment as a fixed effect. 9999=Data Not Available (N/A)
    End point type
    Primary
    End point timeframe
    Baseline, 26 weeks
    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: Zero total participants were analyzed for this End point; statistical analysis was not completed.
    End point values
    		 15 mg LY2886721 35 mg LY2886721 70 mg LY2886721 Placebo
    Number of subjects analysed
    0 [2]
    0 [3]
    0 [4]
    0 [5]
    Units: percent change in Aβ1-40 and Aβ1-42
        least squares mean (standard error)
    ±
    ±
    ±
    ±
    Notes
    [2] - No participants analyzed at 26 weeks due to the termination of the trial.
    [3] - No participants analyzed at 26 weeks due to the termination of the trial.
    [4] - No participants analyzed at 26 weeks due to the termination of the trial.
    [5] - No participants analyzed at 26 weeks due to the termination of the trial.
    No statistical analyses for this end point

    Secondary: Change from Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations

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    End point title
    		 Change from Baseline in Plasma Amyloid Beta (Aβ)1-40 and Aβ1-42 Concentrations
    End point description
    Percent change in plasma concentrations of Aβ1-40 and Aβ1-42 from baseline at 12 weeks and 26 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL). Analysis Population Description: All randomized participants with evaluable post-baseline CSF Aβ1-40 or Aβ1-42 data. 9999=Data Not Available (N/A)
    End point type
    Secondary
    End point timeframe
    Baseline, 12 weeks, 26 weeks
    End point values
    		 15 mg LY2886721 35 mg LY2886721 70 mg LY2886721 Placebo
    Number of subjects analysed
    6
    8
    4 [6]
    12
    Units: percent change in Aβ1-40 and Aβ1-42
    arithmetic mean (standard deviation)
        Aβ1-40, Week 12 (n=6, 8, 4, 12)
    -73.4 ± 6.22
    -80.8 ± 8.07
    -88.1 ± 2.66
    1.9 ± 15
        Aβ1-40, Week 26 (n=5, 6, 1, 6)
    -72.3 ± 11.5
    -85 ± 3.89
    -89.1 ± 9999
    0.944 ± 22.6
        Aβ1-42, Week 12 (n=6, 8, 4, 12
    -63.4 ± 6.11
    -71.1 ± 8.38
    -78.2 ± 5.08
    0.541 ± 10.1
        Aβ1-42, Week 26 (n=5, 6, 1, 6)
    -65.1 ± 8.85
    -75 ± 4.33
    -80.8 ± 9999
    1.82 ± 9.98
    Notes
    [6] - Standard deviation not reported due to not enough participants for analyses.
    No statistical analyses for this end point

    Secondary: Change from Baseline to 26 Weeks in Neuropsychological Test Battery (NTB)

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    End point title
    		 Change from Baseline to 26 Weeks in Neuropsychological Test Battery (NTB)
    End point description
    The NTB is a composite cognitive measure in clinical Alzheimer’s disease studies and is a collection of several written and oral tests that examines verbal and nonverbal brain functions. Lower scores indicate greater cognitive impairment. LS means were calculated using ANCOVA with baseline as a covariate and treatment as a fixed effect. Analysis Population Description: All randomized participants with evaluable NTB data.
    End point type
    Secondary
    End point timeframe
    Baseline, 26 weeks
    End point values
    		 15 mg LY2886721 35 mg LY2886721 70 mg LY2886721 Placebo
    Number of subjects analysed
    8
    7
    1
    9
    Units: units on a scale
    least squares mean (standard error)
        NTB z-score
    -0.039 ± 0.1096
    -0.161 ± 0.1165
    0.424 ± 0.3156
    -0.262 ± 0.1028
        NTB total score
    2 ± 4.77
    -5.9 ± 5.09
    21.2 ± 13.69
    -14.9 ± 4.49
    No statistical analyses for this end point

    Secondary: Change from Baseline to 26 Weeks in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)

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    End point title
    		 Change from Baseline to 26 Weeks in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog)
    End point description
    ADAS-Cog11 is an 11-item instrument measuring impairment in memory (Items 1-4, 7, 11), praxis (Items 4 and 5), orientation (Item 6), and language (Items 8-10). Item 1 ranged 0 (all items recalled correctly)-10 (none recalled correctly); Items 2-5 and 8-11 ranged 0 (all items named, performed, drawn, spoken, remember correctly/clearly)-5 (none correct/not clearly spoken); Item 6 ranged 0 (no incorrect responses)-8 (all incorrect); and Item 7 ranged 0 (all words remembered correctly)-12 (no words remembered correctly) for a total ADAS-Cog11 score of 0-70 with higher scores indicating greater disease severity. A score of 0-10 for delayed free recall and a conversion code of 0-5 for digit cancellation and maze completion was added to the total ADAS-Cog11 score for a total ADAS‑Cog14 score ranging 0-90 with higher scores indicating greater impairment. LS means were calculated using Mixed Model Repeated Measures (MMRM) with Treatment + Visit + Treatment*Visit + Baseline + Baseline*Visit.
    End point type
    Secondary
    End point timeframe
    Baseline, 26 weeks
    End point values
    		 15 mg LY2886721 35 mg LY2886721 70 mg LY2886721 Placebo
    Number of subjects analysed
    7 [7]
    9 [8]
    1 [9]
    9 [10]
    Units: units on a scale
        least squares mean (standard error)
    1.1 ± 2.77
    0.6 ± 2.48
    0.6 ± 7.41
    1.3 ± 2.44
    Notes
    [7] - All randomized participants with evaluable ADAS-Cog data.
    [8] - All randomized participants with evaluable ADAS-Cog data.
    [9] - All randomized participants with evaluable ADAS-Cog data.
    [10] - All randomized participants with evaluable ADAS-Cog data.
    No statistical analyses for this end point

    Secondary: Change from Baseline to 26 Weeks in the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)

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    End point title
    		 Change from Baseline to 26 Weeks in the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)
    End point description
    The CDR-SB is a composite measure of 6 domains of cognitive and functional performance: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Scores ranged from 0 to 18, with higher scores indicating greater impairment. LS means were calculated using MMRM with Treatment + Visit + Treatment*Visit + Baseline + Baseline*Visit. Analysis Population Description: All randomized participants with evaluable CDR-SB data.
    End point type
    Secondary
    End point timeframe
    Baseline, 26 weeks
    End point values
    		 15 mg LY2886721 35 mg LY2886721 70 mg LY2886721 Placebo
    Number of subjects analysed
    8
    9
    1
    8
    Units: units on a scale
        least squares mean (standard error)
    0.8 ± 0.432
    0.52 ± 0.395
    1.5 ± 1.013
    1.19 ± 0.402
    No statistical analyses for this end point

    Secondary: Change from Baseline to 26 Weeks in Mini Mental State Examination (MMSE)

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    End point title
    		 Change from Baseline to 26 Weeks in Mini Mental State Examination (MMSE)
    End point description
    The MMSE (Folstein et al. 1975) is one of the most widely used screening instruments for cognitive impairment. The test consists of five sections (orientation, registration, attention-calculation, recall, and language) and provides a total score ranging from 0 to 30, with lower scores indicative of greater cognitive impairment. LS means were calculated using MMRM with Treatment + Visit + Treatment*Visit + Baseline + Baseline*Visit. Analysis Population Description: All randomized participants with evaluable MMSE data.
    End point type
    Secondary
    End point timeframe
    Baseline, 26 weeks
    End point values
    		 15 mg LY2886721 35 mg LY2886721 70 mg LY2886721 Placebo
    Number of subjects analysed
    8
    9
    1
    10
    Units: units on a scale
        least squares mean (standard error)
    -0.7 ± 0.87
    -1.8 ± 0.81
    0.2 ± 2.41
    -3 ± 0.77
    No statistical analyses for this end point

    Secondary: Change from Baseline in Cerebrospinal Fluid (CSF) Tau and Phosphorylated Tau (Ptau)-181 Concentrations

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    End point title
    		 Change from Baseline in Cerebrospinal Fluid (CSF) Tau and Phosphorylated Tau (Ptau)-181 Concentrations
    End point description
    Percent change in lumbar CSF tau and ptau-181 concentrations from baseline at 12 weeks post-dose and 26 weeks post-dose was calculated. The units for CSF were picograms per milliliter (pg/mL). Least Squares (LS) means of percent change in concentration from baseline was calculated using analysis of covariance (ANCOVA) with baseline as a covariate and treatment as a fixed effect. Analysis Population Description: All randomized participants with evaluable post-baseline CSF tau or ptau data. 9999=Data Not Available (N/A)
    End point type
    Secondary
    End point timeframe
    Baseline, 12 weeks, 26 weeks
    End point values
    		 15 mg LY2886721 35 mg LY2886721 70 mg LY2886721 Placebo
    Number of subjects analysed
    7 [11]
    9 [12]
    5 [13]
    12 [14]
    Units: percent change in tau and ptau-181
    least squares mean (standard error)
        CSF Tau, Week 12
    14.3 ± 6.06
    2.6 ± 5.42
    6.8 ± 7.49
    -4.4 ± 4.63
        CSF Tau, Week 26
    9999 ± 9999
    9999 ± 9999
    9999 ± 9999
    9999 ± 9999
        CSF Ptau, Week 12
    0.7 ± 4.81
    1.7 ± 4.01
    4.3 ± 5.41
    -3.6 ± 3.4
        CSF Ptau, Week 26
    9999 ± 9999
    9999 ± 9999
    9999 ± 9999
    9999 ± 9999
    Notes
    [11] - No participants analyzed at 26 weeks due to the termination of the trial.
    [12] - No participants analyzed at 26 weeks due to the termination of the trial.
    [13] - No participants analyzed at 26 weeks due to the termination of the trial.
    [14] - No participants analyzed at 26 weeks due to the termination of the trial.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Entire Study
    Adverse event reporting additional description
    I4O-MC-BACC
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    15 mg LY2886721
    Reporting group description
    		 -

    Reporting group title
    35 mg LY2886721
    Reporting group description
    		 -

    Reporting group title
    70 mg LY2886721
    Reporting group description
    		 -

    Serious adverse events
    		 Placebo 15 mg LY2886721 35 mg LY2886721 70 mg LY2886721
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    2 / 23 (8.70%)
    0 / 18 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Nervous system disorders
    syncope
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (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
    Gastrointestinal disorders
    crohn's disease
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (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
    small intestinal obstruction
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (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: 0%
    Non-serious adverse events
    		 Placebo 15 mg LY2886721 35 mg LY2886721 70 mg LY2886721
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    15 / 20 (75.00%)
    8 / 9 (88.89%)
    13 / 23 (56.52%)
    16 / 18 (88.89%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    basal cell carcinoma
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    squamous cell carcinoma of skin
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vascular disorders
    hypertension
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    fatigue
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    oedema peripheral
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    pyrexia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    thirst
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Psychiatric disorders
    abnormal dreams
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    agitation
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    anxiety
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    confusional state
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    1
    0
    0
    1
    delusion
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    1
    0
    depression
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    3 / 18 (16.67%)
         occurrences all number
    0
    0
    0
    3
    disorientation
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    hallucination
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    hallucination, visual
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    hypnopompic hallucination
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    initial insomnia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    insomnia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 9 (11.11%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    1
    1
    2
    0
    nightmare
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    obsessive thoughts
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    parasomnia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    restlessness
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    sleep talking
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    stereotypy
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    terminal insomnia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Investigations
    alanine aminotransferase increased
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    amylase increased
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    blood alkaline phosphatase increased
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    blood creatine phosphokinase increased
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    2
    0
    0
    0
    blood pressure increased
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    colour vision tests abnormal red-green
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    electrocardiogram change
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    gamma-glutamyltransferase increased
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    3 / 18 (16.67%)
         occurrences all number
    0
    1
    0
    3
    lipase increased
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    1
    2
    liver function test abnormal
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    2 / 23 (8.70%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    2
    1
    weight increased
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Injury, poisoning and procedural complications
    accidental overdose
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    alcohol poisoning
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    contusion
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    fall
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    2 / 18 (11.11%)
         occurrences all number
    1
    0
    1
    3
    feeding tube complication
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    foot fracture
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    joint injury
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    laceration
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    2 / 18 (11.11%)
         occurrences all number
    1
    0
    0
    3
    tooth fracture
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    Cardiac disorders
    atrial fibrillation
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    bradycardia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nervous system disorders
    apraxia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    balance disorder
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    cerebral microhaemorrhage
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    decreased vibratory sense
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    dizziness
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    1
    0
    0
    dysgeusia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    headache
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 9 (22.22%)
    1 / 23 (4.35%)
    1 / 18 (5.56%)
         occurrences all number
    0
    2
    1
    1
    sinus headache
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    4
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    leukocytosis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Ear and labyrinth disorders
    vertigo
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Eye disorders
    cataract nuclear
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    diplopia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    eye irritation
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    lacrimation increased
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    visual acuity reduced
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastrointestinal disorders
    abdominal discomfort
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    2
    0
    abdominal distension
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    abdominal pain upper
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    abdominal tenderness
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    dental caries
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    diarrhoea
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    1 / 18 (5.56%)
         occurrences all number
    1
    0
    1
    1
    diverticulum intestinal
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    2
    0
    0
    0
    dry mouth
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    flatulence
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    gastritis erosive
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    gastrointestinal disorder
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    2
    0
    0
    0
    gastrooesophageal reflux disease
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    haematochezia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    haemorrhoidal haemorrhage
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    haemorrhoids
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    hiatus hernia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    lip swelling
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    nausea
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    oesophageal disorder
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    oesophagitis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    small intestinal obstruction
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    vomiting
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    2 / 20 (10.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Hepatobiliary disorders
    hepatic function abnormal
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    actinic keratosis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    2
    0
    0
    eczema
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    rash
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    rash macular
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    rash vesicular
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    urticaria
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Renal and urinary disorders
    cystitis interstitial
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    pollakiuria
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    0
    1
    renal failure chronic
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    Endocrine disorders
    hypothyroidism
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    back pain
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    1
    0
    0
    2
    joint range of motion decreased
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    joint swelling
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    muscle spasms
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    1 / 18 (5.56%)
         occurrences all number
    2
    0
    1
    1
    muscle tightness
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    0
    0
    musculoskeletal chest pain
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    2
    0
    0
    0
    musculoskeletal stiffness
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    Infections and infestations
    herpes zoster
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1
    nasopharyngitis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    sinusitis
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    upper respiratory tract infection
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 9 (11.11%)
    1 / 23 (4.35%)
    1 / 18 (5.56%)
         occurrences all number
    1
    1
    1
    1
    urinary tract infection
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 9 (11.11%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Metabolism and nutrition disorders
    decreased appetite
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    dehydration
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    0 / 18 (0.00%)
         occurrences all number
    1
    0
    0
    0
    hypokalaemia
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    1 / 23 (4.35%)
    0 / 18 (0.00%)
         occurrences all number
    0
    0
    1
    0
    increased appetite
    alternative dictionary used: MedDRA 16.0
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 9 (0.00%)
    0 / 23 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    0
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Oct 2012
    Amendment B: Added the 70 mg dose and dropped the 15 mg dose. Added change in CSF tau and p-tau181 as secondary outcomes.
    08 Apr 2013
    Amendment C: Clarified the purpose of the study as a Ph2a PK/PD/safety study. Revised diagnostic criteria to align with contemporary clinical practice. Removed florbetapir scan at Visit 11. Alterations to inclusion/exclusion criteria. Added discontinuation criteria for patients with abnormal liver tests. Altered the randomization ratio to increase the number of subjects assigned to 70 mg dose.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    12 Jun 2013
    The study was terminated early due to hepatic safety finding.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Study was terminated early because of abnormal liver biochemical tests levels for 4 participants.
    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.

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