Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A randomized, double-blind, placebo-controlled, parallel-group study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple oral doses of CNP520 in healthy elderly subjects

    Summary
    EudraCT number
    		 2013-005576-18
    Trial protocol
    		 NL   DE   BE   GB  
    Global end of trial date
    11 Mar 2016

    Results information
    Results version number
    		 v2(current)
    This version publication date
    10 Jun 2017
    First version publication date
    25 Mar 2017
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    For the PK secondary end points, AUCtau and Tmax, the small 'n' for the CNP520 10 mg group of day 91 had to be corrected to '23'.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CCNP520X2102
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma, AG, +41 61324 1111,
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma, AG, +41 61324 1111,
    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
    11 Mar 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Mar 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the safety and tolerability of multiple, once-daily oral doses of CNP520 over 13 weeks in healthy elderly subjects.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Aug 2015
    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: 55
    Country: Number of subjects enrolled
    Netherlands: 29
    Country: Number of subjects enrolled
    United Kingdom: 20
    Country: Number of subjects enrolled
    Belgium: 10
    Country: Number of subjects enrolled
    Germany: 10
    Worldwide total number of subjects
    124
    EEA total number of subjects
    69
    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)
    52
    From 65 to 84 years
    72
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants were randomized in a 1:1:1:1:1 ratio to 5 treatment groups: placebo, CNP520 2 mg, CNP520 10 mg, CNP520 35 mg and CNP520 85 mg.

    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, Monitor, Data analyst

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Matching placebo to CNP520 was taken once daily (qd) orally for 13 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
    Matching placebo qd orally (2 capsules of placebo)

    Arm title
    		 CNP520 2 mg
    Arm description
    		 CNP520 2 mg was taken qd orally for 13 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CNP520
    Investigational medicinal product code
    CNP520
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    CNP520 2 mg qd (2 capsules of 1 mg CNP520)

    Arm title
    		 CNP520 10 mg
    Arm description
    		 CNP520 10 mg was taken qd orally for 13 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CNP520
    Investigational medicinal product code
    CNP520
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    CNP520 10 mg qd (1 capsule of CNP520 10 mg and 1 capsule of placebo)

    Arm title
    		 CNP520 35 mg
    Arm description
    		 CNP520 35 mg was taken qd orally for 13 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CNP520
    Investigational medicinal product code
    CNP520
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    CNP520 35 mg qd (1 capsule of 25 mg CNP520 and 1 capsule of CNP520 10 mg)

    Arm title
    		 CNP520 85 mg
    Arm description
    		 CNP520 85 mg was taken qd orally for 13 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    CNP520
    Investigational medicinal product code
    CNP520
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    CNP520 85 mg qd (1 capsule of CNP520 75 mg and 1 capsule of CNP520 10 mg)

    Number of subjects in period 1
    		Placebo CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Started
    24
    25
    25
    26
    24
    Safety analysis set
    24
    25
    25
    26
    24
    Pharmacokinetic analysis set
    0 [1]
    25
    25
    26
    24
    Pharmacodynamic analysis set
    24
    24
    25
    25
    24
    Completed
    22
    23
    23
    25
    20
    Not completed
    2
    2
    2
    1
    4
         Consent withdrawn by subject
    1
    2
    1
    -
    1
         Physician decision
    -
    -
    -
    -
    1
         Adverse event, non-fatal
    1
    -
    1
    1
    2
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: The number of subjects is correct.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Matching placebo to CNP520 was taken once daily (qd) orally for 13 weeks.

    Reporting group title
    CNP520 2 mg
    Reporting group description
    		 CNP520 2 mg was taken qd orally for 13 weeks.

    Reporting group title
    CNP520 10 mg
    Reporting group description
    		 CNP520 10 mg was taken qd orally for 13 weeks.

    Reporting group title
    CNP520 35 mg
    Reporting group description
    		 CNP520 35 mg was taken qd orally for 13 weeks.

    Reporting group title
    CNP520 85 mg
    Reporting group description
    		 CNP520 85 mg was taken qd orally for 13 weeks.

    Reporting group values
    		 Placebo CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg Total
    Number of subjects
    		 24 25 25 26 24 124
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0
        Adults (18-64 years)
    		 11 12 8 10 11 52
        From 65-84 years
    		 13 13 17 16 13 72
        85 years and over
    		 0 0 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 66.6 ( 5.3 ) 65.4 ( 4.6 ) 66.8 ( 5.1 ) 66.1 ( 4.6 ) 66.5 ( 5.2 ) -
    Gender categorical
    Units: Subjects
        Female
    		 12 16 13 11 9 61
        Male
    		 12 9 12 15 15 63

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Matching placebo to CNP520 was taken once daily (qd) orally for 13 weeks.

    Reporting group title
    CNP520 2 mg
    Reporting group description
    		 CNP520 2 mg was taken qd orally for 13 weeks.

    Reporting group title
    CNP520 10 mg
    Reporting group description
    		 CNP520 10 mg was taken qd orally for 13 weeks.

    Reporting group title
    CNP520 35 mg
    Reporting group description
    		 CNP520 35 mg was taken qd orally for 13 weeks.

    Reporting group title
    CNP520 85 mg
    Reporting group description
    		 CNP520 85 mg was taken qd orally for 13 weeks.

    Primary: Number of participants with non-serious and serious adverse events (AEs) and deaths

    		 Close Top of page
    End point title
    		 Number of participants with non-serious and serious adverse events (AEs) and deaths [1]
    End point description
    Safety monitoring was conducted throughout the study.
    End point type
    Primary
    End point timeframe
    13 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: Statistical analysis does not apply to this end point.
    End point values
    		 Placebo CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Number of subjects analysed
    24
    25
    25
    26
    24
    Units: Participants
        Non-serious AEs
    18
    19
    22
    20
    18
        Serious AEs
    0
    0
    0
    1
    0
        Deaths
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Change from baseline in of amyloid beta (Aβ) 1-38, Aβ 1-40 and Aβ 1-42 cerebospinal fluid (CSF) concentrations

    		 Close Top of page
    End point title
    		 Change from baseline in of amyloid beta (Aβ) 1-38, Aβ 1-40 and Aβ 1-42 cerebospinal fluid (CSF) concentrations
    End point description
    CSF samples were collected by lumbar puncture for assessment. The pharmacodynamics (PD) analysis set was analyzed. The PD set included only randomized participants who had available PD data and no protocol deviations with relevant impact on PD data.
    End point type
    Secondary
    End point timeframe
    Day 92
    End point values
    		 Placebo CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Number of subjects analysed
    21
    22
    21
    23
    20
    Units: Percentage
    arithmetic mean (standard deviation)
        Aβ 1-38
    -2.34 ( 6.969 )
    -20.55 ( 10.475 )
    -62.48 ( 6.202 )
    -82.93 ( 4.378 )
    -89.5 ( 1.676 )
        Aβ 1-40
    -2.64 ( 6.598 )
    -22.64 ( 9.937 )
    -62.89 ( 6.485 )
    -83.16 ( 4.227 )
    -90.69 ( 1.651 )
        Aβ 1-42
    -2.58 ( 5.189 )
    -23.93 ( 8.987 )
    -64.28 ( 6.086 )
    -82.35 ( 5.474 )
    -89.68 ( 2.32 )
    No statistical analyses for this end point

    Secondary: Summary of plasma PK parameter: Cmax

    		 Close Top of page
    End point title
    		 Summary of plasma PK parameter: Cmax [2]
    End point description
    Cmax = the observed maximum plasma concentration following drug administration. Blood samples were collected to assess Cmax. The PK analysis set was used for the analysis. For a given time point, only those participants from the PK analysis set, who had PK data and had no protocol deviations with relevant impact on PK data, were analyzed for that time point.
    End point type
    Secondary
    End point timeframe
    Days 1, 91
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: All arms do not apply to this end point.
    End point values
    		 CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Number of subjects analysed
    25
    25
    26
    24
    Units: ng/mL
    arithmetic mean (standard deviation)
        Day 1 (n=25,25,26,24)
    4.76 ( 2.92 )
    21.3 ( 6.67 )
    75.6 ( 23.4 )
    163 ( 47.4 )
        Day 91 (=23,22,24,20)
    16.6 ( 5.51 )
    81 ( 29.2 )
    237 ( 65.7 )
    602 ( 150 )
    No statistical analyses for this end point

    Secondary: Summary of plasma PK parameter: AUCtau

    		 Close Top of page
    End point title
    		 Summary of plasma PK parameter: AUCtau [3]
    End point description
    AUCtau = the area under the plasma concentration-time curve from zero to the end of the dosing interval tau. Blood samples were collected to assess AUCtau. The PK analysis set was used for the analysis. For a given time point, only those participants from the PK analysis set, who had PK data and had no protocol deviations with relevant impact on PK data, were analyzed for that time point.
    End point type
    Secondary
    End point timeframe
    Days 1 and 91
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: All arms do not apply to this end point.
    End point values
    		 CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Number of subjects analysed
    25
    25
    26
    24
    Units: h*ng/mL
    arithmetic mean (standard deviation)
        Day 1 (n=25,25,26,24)
    67.1 ( 60.7 )
    278 ( 65.7 )
    966 ( 214 )
    2300 ( 479 )
        Day 91 (n=23,22,24,20)
    313 ( 117 )
    1500 ( 476 )
    4450 ( 1090 )
    11200 ( 3320 )
    No statistical analyses for this end point

    Secondary: Summary of plasma PK parameter: Tmax

    		 Close Top of page
    End point title
    		 Summary of plasma PK parameter: Tmax [4]
    End point description
    Tmax = the time to reach the maximum concentration after drug administration. Blood samples were collected to assess Tmax. The PK analysis set was used for the analysis. For a given time point, only those participants from the PK analysis set, who had PK data and had no protocol deviations with relevant impact on PK data, were analyzed for that time point.
    End point type
    Secondary
    End point timeframe
    Days 1 and 91
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: All arms do not apply to this end point.
    End point values
    		 CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Number of subjects analysed
    25
    25
    26
    24
    Units: hour
    median (full range (min-max))
        Day 1 (n=25,25,26,24)
    2.5 (2.45 to 9)
    2.5 (2.5 to 6.02)
    2.5 (2.48 to 9)
    2.5 (2.42 to 12)
        Day 91 (n=23,22,24,20)
    2.5 (0 to 12.1)
    2.5 (0 to 12.5)
    2.5 (0 to 12)
    2.5 (0 to 12)
    No statistical analyses for this end point

    Secondary: Summary of plasma PK parameter: Tlag

    		 Close Top of page
    End point title
    		 Summary of plasma PK parameter: Tlag [5]
    End point description
    Tlag = time delay between drug administration and first observed concentration above the lower limit of quantification (LOQ) in plasma . Blood samples were collected to assess Tlag. The PK analysis set was used for the analysis. For a given time point, only those participants from the PK analysis set, who had PK data and had no protocol deviations with relevant impact on PK data, were analyzed for that time point.
    End point type
    Secondary
    End point timeframe
    Days 1 and 91
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: All arms do not apply to this end point.
    End point values
    		 CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Number of subjects analysed
    25
    25
    26
    24
    Units: hour
    median (full range (min-max))
        Day 1 (n=25,25,26,24)
    0.5 (0 to 0.567)
    0.5 (0 to 2.5)
    0.5 (0 to 0.55)
    0 (0 to 2.5)
        Day 91 (n=23,22,24,20)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    0 (0 to 0)
    No statistical analyses for this end point

    Secondary: Summary of plasma PK parameter: T1/2

    		 Close Top of page
    End point title
    		 Summary of plasma PK parameter: T1/2 [6]
    End point description
    T1/2 = the terminal elimination half-life. Blood samples were collected to assess T/12. The PK analysis set was used for the analysis. Only those participants from the PK analysis set, who had PK data and had no protocol deviations with relevant impact on PK data, were analyzed.
    End point type
    Secondary
    End point timeframe
    Day 91
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: All arms do not apply to this end point.
    End point values
    		 CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Number of subjects analysed
    23
    22
    24
    20
    Units: hour
        arithmetic mean (standard deviation)
    150 ( 52.2 )
    155 ( 40.9 )
    155 ( 33.9 )
    160 ( 22 )
    No statistical analyses for this end point

    Secondary: Summary of PK parameter: CLss/F

    		 Close Top of page
    End point title
    		 Summary of PK parameter: CLss/F [7]
    End point description
    CLss/F = the apparent systemic clearance from plasma observed during a dosing interval at steady state following extravascular administration. Blood samples were collected to assess CLss/F. The PK analysis set was used for the analysis. Only those participants from the PK analysis set, who had PK data and had no protocol deviations with relevant impact on PK data, were analyzed.
    End point type
    Secondary
    End point timeframe
    Day 91
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: All arms do not apply to this end point.
    End point values
    		 CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Number of subjects analysed
    23
    22
    24
    20
    Units: mL/h
        arithmetic mean (standard deviation)
    7260 ( 2620 )
    7380 ( 2480 )
    8460 ( 2790 )
    8220 ( 2270 )
    No statistical analyses for this end point

    Secondary: Summary of plasma PK parameter: Racc

    		 Close Top of page
    End point title
    		 Summary of plasma PK parameter: Racc [8]
    End point description
    Racc = the accumulation ratio . Blood samples were collected to assess Racc. The PK analysis set was used for the analysis. Only those participants from the PK analysis set, who had PK data and had no protocol deviations with relevant impact on PK data, were analyzed.
    End point type
    Secondary
    End point timeframe
    Day 91
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: All arms do not apply to this end point.
    End point values
    		 CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Number of subjects analysed
    23
    22
    24
    20
    Units: ratio
        arithmetic mean (standard deviation)
    5.86 ( 2.25 )
    5.33 ( 1.05 )
    4.75 ( 1.16 )
    5.02 ( 1.47 )
    No statistical analyses for this end point

    Secondary: Summary of CSF PK concentrations

    		 Close Top of page
    End point title
    		 Summary of CSF PK concentrations [9]
    End point description
    CSF samples were collected by lumbar puncture for assessment. The PK analysis set was used for the analysis. For a given time point, only those participants from the PK analysis set, who had PK data and had no protocol deviations with relevant impact on PK data, were analyzed for that time point.
    End point type
    Secondary
    End point timeframe
    Days 1, 14, 28, 42, 56, 70 and 91
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: All arms do not apply to this end point.
    End point values
    		 CNP520 2 mg CNP520 10 mg CNP520 35 mg CNP520 85 mg
    Number of subjects analysed
    25
    25
    26
    24
    Units: ng/mL
    arithmetic mean (standard deviation)
        Day 1 (n=24,25,26,24)
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
        Day 14 (n=3,4,4,4)
    0.116 ( 0.103 )
    1.07 ( 0.225 )
    3.82 ( 0.868 )
    8.13 ( 2.7 )
        Day 28 (n=5,2,7,5)
    0.303 ( 0.0731 )
    1.48 ( 0.106 )
    4.48 ( 1.02 )
    12 ( 4.12 )
        Day 42 (n=3,6,5,5)
    0.314 ( 0.0715 )
    1.52 ( 0.6 )
    4 ( 1.21 )
    7.47 ( 1.57 )
        Day 56 (n=5,5,2,4)
    0.291 ( 0.0605 )
    1.28 ( 0.177 )
    5.03 ( 2.69 )
    8.04 ( 5.69 )
        Day 70 (n=6,5,6,4)
    0.231 ( 0.149 )
    1.04 ( 0.212 )
    4.62 ( 0.753 )
    8.71 ( 0.71 )
        Day 91 (n=23,21,24,20)
    0.305 ( 0.099 )
    1.44 ( 0.431 )
    4.52 ( 0.946 )
    10.4 ( 3.26 )
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Placebo

    Reporting group title
    CNP520 2mg
    Reporting group description
    		 CNP520 2mg

    Reporting group title
    CNP520 10mg
    Reporting group description
    		 CNP520 10mg

    Reporting group title
    CNP520 35mg
    Reporting group description
    		 CNP520 35mg

    Reporting group title
    CNP520 85mg
    Reporting group description
    		 CNP520 85mg

    Serious adverse events
    		 Placebo CNP520 2mg CNP520 10mg CNP520 35mg CNP520 85mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo CNP520 2mg CNP520 10mg CNP520 35mg CNP520 85mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    18 / 24 (75.00%)
    19 / 25 (76.00%)
    22 / 25 (88.00%)
    20 / 26 (76.92%)
    18 / 24 (75.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Seborrhoeic keratosis
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    Vascular disorders
    Flushing
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    1
    0
    1
    Hot flush
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Fatigue
         subjects affected / exposed
    3 / 24 (12.50%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    2 / 26 (7.69%)
    2 / 24 (8.33%)
         occurrences all number
    5
    0
    0
    2
    2
    Feeling cold
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Influenza like illness
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    0
    2
    1
    Injection site pain
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    2 / 24 (8.33%)
         occurrences all number
    0
    0
    0
    1
    2
    Pain
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Puncture site pain
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    1 / 25 (4.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    Vessel puncture site haemorrhage
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    2
    0
    0
    Vessel puncture site pain
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Vessel puncture site swelling
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Immune system disorders
    Allergy to chemicals
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    0
    0
    1
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Erectile dysfunction
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Pruritus genital
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 24 (4.17%)
    2 / 25 (8.00%)
    3 / 25 (12.00%)
    3 / 26 (11.54%)
    3 / 24 (12.50%)
         occurrences all number
    1
    2
    4
    4
    3
    Dysphonia
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    Dyspnoea
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Epistaxis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Hiccups
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Nasal congestion
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    2
    0
    1
    1
    1
    Oropharyngeal pain
         subjects affected / exposed
    4 / 24 (16.67%)
    2 / 25 (8.00%)
    2 / 25 (8.00%)
    2 / 26 (7.69%)
    0 / 24 (0.00%)
         occurrences all number
    4
    2
    2
    2
    0
    Productive cough
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    1
    0
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 25 (0.00%)
    2 / 25 (8.00%)
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    2
    0
    2
    1
    2
    Sinus congestion
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    1
    0
    2
    Throat irritation
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    1
    0
    2
    Psychiatric disorders
    Abnormal dreams
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    1 / 25 (4.00%)
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    2
    1
    1
    Affective disorder
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    0
    0
    1
    Confusional state
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Irritability
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Libido decreased
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Nightmare
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    0
    0
    1
    Obsessive thoughts
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Investigations
    Amylase increased
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    2
    0
    0
    1
    Blood bilirubin increased
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Blood cholesterol increased
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 24 (0.00%)
    2 / 25 (8.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Blood triglycerides increased
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Lipase increased
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Contusion
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Ear abrasion
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Foreign body in eye
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Joint dislocation
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Laceration
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    2 / 26 (7.69%)
    1 / 24 (4.17%)
         occurrences all number
    1
    0
    1
    2
    1
    Ligament sprain
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Limb injury
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Post lumbar puncture syndrome
         subjects affected / exposed
    8 / 24 (33.33%)
    2 / 25 (8.00%)
    1 / 25 (4.00%)
    3 / 26 (11.54%)
    3 / 24 (12.50%)
         occurrences all number
    9
    3
    1
    3
    3
    Post procedural discomfort
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    2 / 25 (8.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    2
    1
    0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Procedural complication
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    1
    0
    1
    0
    1
    Procedural dizziness
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 25 (0.00%)
    3 / 25 (12.00%)
    2 / 26 (7.69%)
    0 / 24 (0.00%)
         occurrences all number
    3
    0
    3
    2
    0
    Procedural nausea
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    1
    0
    0
    1
    1
    Procedural pain
         subjects affected / exposed
    1 / 24 (4.17%)
    3 / 25 (12.00%)
    4 / 25 (16.00%)
    2 / 26 (7.69%)
    3 / 24 (12.50%)
         occurrences all number
    1
    4
    4
    3
    3
    Scratch
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Skin abrasion
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Thermal burn
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    1
    0
    0
    0
    2
    Traumatic lumbar puncture
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Wound complication
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    0
    0
    1
    Nervous system disorders
    Amnesia
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    1
    0
    2
    Balance disorder
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    1
    0
    1
    Cognitive disorder
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Dizziness
         subjects affected / exposed
    3 / 24 (12.50%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    3
    0
    7
    1
    0
    Dizziness postural
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Dysarthria
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Dysgeusia
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Head discomfort
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 25 (4.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    Headache
         subjects affected / exposed
    10 / 24 (41.67%)
    11 / 25 (44.00%)
    5 / 25 (20.00%)
    5 / 26 (19.23%)
    5 / 24 (20.83%)
         occurrences all number
    16
    16
    7
    11
    11
    Lethargy
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    0
    0
    1
    Neuropathy peripheral
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Presyncope
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Sedation
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Sinus headache
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    Somnolence
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    2 / 26 (7.69%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    0
    2
    1
    Syncope
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Tension headache
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Visual field defect
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Blood and lymphatic system disorders
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Ear and labyrinth disorders
    Ear discomfort
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    0
    0
    1
    Ear pain
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Eustachian tube dysfunction
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Tinnitus
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Eye disorders
    Asthenopia
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Dry eye
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    0
    0
    1
    Eye irritation
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    0
    0
    1
    Eye pain
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    4
    0
    0
    Eye pruritus
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    2 / 25 (8.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    2
    0
    1
    Lacrimation increased
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Ocular hyperaemia
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    0
    0
    1
    Vision blurred
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 25 (4.00%)
    2 / 25 (8.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    1
    1
    5
    0
    1
    Visual impairment
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Abdominal pain
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    2
    0
    1
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Constipation
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    1 / 25 (4.00%)
    2 / 26 (7.69%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    1
    2
    2
    Diarrhoea
         subjects affected / exposed
    5 / 24 (20.83%)
    1 / 25 (4.00%)
    3 / 25 (12.00%)
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    8
    1
    5
    2
    1
    Dry mouth
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Dyspepsia
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    2 / 25 (8.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    2
    1
    0
    Eructation
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Faeces hard
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Faeces soft
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Flatulence
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 25 (4.00%)
    3 / 25 (12.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    1
    4
    1
    0
    Frequent bowel movements
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Glossodynia
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Nausea
         subjects affected / exposed
    2 / 24 (8.33%)
    2 / 25 (8.00%)
    3 / 25 (12.00%)
    2 / 26 (7.69%)
    2 / 24 (8.33%)
         occurrences all number
    3
    2
    3
    3
    3
    Toothache
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    1
    0
    2
    3
    2
    Vomiting
         subjects affected / exposed
    1 / 24 (4.17%)
    2 / 25 (8.00%)
    0 / 25 (0.00%)
    2 / 26 (7.69%)
    0 / 24 (0.00%)
         occurrences all number
    2
    2
    0
    2
    0
    Skin and subcutaneous tissue disorders
    Cold sweat
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Dermatitis
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    0
    0
    1
    Dermatitis contact
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    1
    0
    2
    Dry skin
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    Ecchymosis
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    0
    0
    0
    2
    Erythema
         subjects affected / exposed
    0 / 24 (0.00%)
    2 / 25 (8.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    3 / 25 (12.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    Pruritus generalised
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    2 / 25 (8.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    1
    4
    0
    1
    Psoriasis
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    0
    0
    2
    Rash
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    Rash papular
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Rash pruritic
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    0
    0
    1
    Renal and urinary disorders
    Micturition urgency
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Pollakiuria
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    2 / 26 (7.69%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    0
    4
    1
    Polyuria
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 24 (4.17%)
    2 / 25 (8.00%)
    3 / 25 (12.00%)
    3 / 26 (11.54%)
    1 / 24 (4.17%)
         occurrences all number
    1
    2
    3
    3
    1
    Back pain
         subjects affected / exposed
    6 / 24 (25.00%)
    2 / 25 (8.00%)
    2 / 25 (8.00%)
    3 / 26 (11.54%)
    4 / 24 (16.67%)
         occurrences all number
    9
    2
    2
    3
    5
    Joint stiffness
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Joint swelling
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Muscle spasms
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    2 / 25 (8.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Muscle tightness
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Muscular weakness
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Musculoskeletal discomfort
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 24 (0.00%)
    2 / 25 (8.00%)
    1 / 25 (4.00%)
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    0
    2
    1
    1
    1
    Musculoskeletal stiffness
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    2
    0
    0
    0
    2
    Myalgia
         subjects affected / exposed
    3 / 24 (12.50%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    2 / 26 (7.69%)
    1 / 24 (4.17%)
         occurrences all number
    3
    0
    0
    2
    4
    Neck pain
         subjects affected / exposed
    1 / 24 (4.17%)
    2 / 25 (8.00%)
    0 / 25 (0.00%)
    1 / 26 (3.85%)
    1 / 24 (4.17%)
         occurrences all number
    1
    2
    0
    2
    1
    Pain in extremity
         subjects affected / exposed
    2 / 24 (8.33%)
    2 / 25 (8.00%)
    1 / 25 (4.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    2
    2
    1
    1
    0
    Plantar fasciitis
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Infections and infestations
    Abscess
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Abscess jaw
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    0
    0
    1
    Bronchitis
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    1
    0
    1
    Hordeolum
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    4 / 24 (16.67%)
    2 / 25 (8.00%)
    5 / 25 (20.00%)
    4 / 26 (15.38%)
    1 / 24 (4.17%)
         occurrences all number
    6
    2
    5
    5
    1
    Oral herpes
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    1 / 24 (4.17%)
         occurrences all number
    0
    0
    0
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Sinusitis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Tinea pedis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 25 (0.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 24 (8.33%)
    1 / 25 (4.00%)
    2 / 25 (8.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    3
    1
    3
    1
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    1 / 26 (3.85%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Metabolism and nutrition disorders
    Gout
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 25 (0.00%)
    1 / 25 (4.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Increased appetite
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 25 (4.00%)
    0 / 25 (0.00%)
    0 / 26 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Aug 2015
    Amendment 1 was issued approximately 4 months after original protocol to address Medicines and Healthcare Products Regulatory Agency (MHRA) requests and at the time of the amendment finalization only 2 subjects were screened and none randomized. Study drug discontinuation criteria were modified such that those listed under the discretion of the Investigator were changed to mandatory individual discontinuation criteria. This amendment introduced the following changes: Section 7.1 Discontinuation of study treatment: The following 4 discontinuation criteria that were under the discretion of the Investigator were changed to mandatory individual discontinuation criteria: • Suspected event of drug-induced renal toxicity based on clinical signs and/or laboratory parameters including an increase of serum creatinine by ≥25% compared to baseline • Major non-compliance with study requirements including drug intake • Indication for increased suicidal risk (as determined by C-SSRS assessments) • QTcF prolongation of >60 msec compared to baseline or QTcF >500 msec As a consequence of this change, the following mandatory discontinuation criterion became redundant and had therefore been removed: • QTcF prolongation of >60 msec compared to baseline in combination with QTcF >500 msec
    13 Oct 2015
    Amendment 2 was made to address comments raised by health authorities and ethics committees in the course of protocol review and IND application. The amendment was issued (when 99 subjects were screened and 44 of these were randomized) and introduced the following key changes: •Addition of an exclusion criterion regarding signs or symptoms of raised intracranial blood pressure and thrombocytopenia. •In addition, it was requested by the UK Ethics committee that a minimum of 24 h stay was required after each lumbar puncture. In the original protocol, a 24 h stay was already included at visits including the first and third lumbar puncture, due to other assessments (eg, PK time course, safety observation after first dosage administration). The Amendment 2 clarified that if required, a 24 h stay post the second lumbar puncture could occur based on local requirements.
    08 Dec 2015
    Amendment 3 was made to address FDA feedback received in context of a pre-IND meeting. This was issued when all 125 subjects were screened and all were randomized. Therefore, an additional Part II was added to this trial primarily in order to assess the PD effects of CNP520 in hetero- and homozygous ApoE4 carriers compared to homozygous ApoE3 subjects as reference group. It introduced the following changes: •An additional Part II was added to this trial primarily in order to assess the PD effects of CNP520 in hetero- and homozygous ApoE4 carriers compared to homozygous ApoE3 subjects as reference group. This Part II was planned to run independently of the core study that would be referred to as Part I. There were no data from Part I that would be required to start Part II or vice versa. However, the Part II of the study was not implemented. • In addition, this amendment clarified that blood cotinine was required only at screening. In all previous protocol versions there was conflicting information.
    11 Mar 2016
    Amendment 4 was made to remove the group of heterozygous ApoE4 carriers in Part II of this clinical study following exploratory genetic analysis of data from CNP520X2101 which indicated no relevant difference of the PD effects of CNP520 in heterozygous ApoE4 carriers compared to wild-type subjects. This amendment was issued when all subjects were screened, randomized and completed the trial and introduced the following changes: •As exploratory genetic analysis of data from the FIH study CCNP520X2101 indicated no relevant difference of the PD effects of CNP520 in heterozygous ApoE4 carriers compared to wild-type subjects, this amendment was made to remove the group of heterozygous ApoE4 carriers in Part II of this clinical study. •In addition, based on preliminary data from the FIH, an increase in plasma 4β-hydroxy cholesterol ratio post-treatment/baseline was observed in the 2-week CNP520 multiple dose part indicating induction of CYP3A4. Measurement of plasma 4β-OH cholesterol was added in this study to evaluate if CNP520 induces CYP3A4 after three months CNP520 treatment at dose levels ranging from 2 mg once daily to 85 mg qd, and an exploratory objective was added to Part I of this study. • Finally, in order to appropriately analyze Part I data and properly design future clinical trials, the protocol clarified that an interim analysis of Part I could be conducted. This interim analysis would take place once all subjects of Part I had completed the trial.

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

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

    European Medicines Agency © 1995-Sat Apr 20 15:41:08 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA