Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   39192   clinical trials with a EudraCT protocol, of which   6421   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).
     
    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 dose finding study to assess the safety and efficacy of K-877 in patients with statin-controlled LDL-C but abnormal lipid levels

    Summary
    EudraCT number
    2013-001517-32
    Trial protocol
    SE   GB   HU   DE   CZ   NL   DK   PL  
    Global end of trial date
    23 Sep 2014

    Results information
    Results version number
    v1(current)
    This version publication date
    01 Apr 2016
    First version publication date
    01 Apr 2016
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    K-877-201
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Kowa Research Europe Ltd
    Sponsor organisation address
    105 Wharfedale Road, Winnersh Triangle, Wokingham, United Kingdom, RG41 5RB
    Public contact
    Regulatory Affairs, Kowa Research Europe Ltd, +44 0118 922 9000,
    Scientific contact
    Regulatory Affairs, Kowa Research Europe Ltd, +44 0118 922 9000,
    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
    20 Oct 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    23 Sep 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Sep 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the dose response of the following parameters: •% change in non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to Week 12 •% change in TG from baseline to Week 12 To assess the safety and tolerability of K-877 in patients with residual cardiovascular risk despite statin-controlled low density lipoprotein (LDL-C) concentration as particularly evaluated by: •Change and % change in serum creatinine from baseline to Week 12 •Change and % change in log(homocysteine) from baseline to Week 12
    Protection of trial subjects
    Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. Each patient was assured of his/her right to withdraw from the study at any time. Close monitoring of all subjects was adhered to throughout the trial conduct. Throughout the study, patients were not allowed to change the dose, dosing regimen (e.g. morning or evening dose), or the type of statin and encouraged to continue on the same diet and exercise regimen. In general, any other medication not excluded by the protocol was permitted.
    Background therapy
    Stable statin therapy (except for pravastatin, lovastatin, and fluvastatin)
    Evidence for comparator
    -
    Actual start date of recruitment
    11 Oct 2013
    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
    Sweden: 19
    Country: Number of subjects enrolled
    United Kingdom: 17
    Country: Number of subjects enrolled
    Czech Republic: 38
    Country: Number of subjects enrolled
    Denmark: 34
    Country: Number of subjects enrolled
    Germany: 4
    Country: Number of subjects enrolled
    Hungary: 93
    Country: Number of subjects enrolled
    Netherlands: 56
    Country: Number of subjects enrolled
    Poland: 31
    Country: Number of subjects enrolled
    Russian Federation: 116
    Worldwide total number of subjects
    408
    EEA total number of subjects
    292
    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)
    273
    From 65 to 84 years
    135
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    The Screening Period was up to a maximum of 4 weeks in duration and consisted of 1 or 2 visits: Screening Visit (SV) 1 for all patients, and SV 2 for patients who failed to meet inclusion criterion #5 (fasting TG ≥175 mg/dL [1.97 mmol/L] and ≤500 mg/dL [5.65 mmol/L]) at SV 1.

    Period 1
    Period 1 title
    Treatment period (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo twice daily
    Arm description
    -
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo tablet
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Two placebo tablets were to be taken orally, twice daily in the morning and the evening. Duration of treatment was 12 weeks.

    Arm title
    K-877 0.05 mg twice daily
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    K-877 0.05 mg tablet
    Investigational medicinal product code
    K-877
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One K-877 0.05 mg tablet and one placebo tablet were to be taken orally, twice daily in the morning and the evening. Duration of treatment was 12 weeks.

    Investigational medicinal product name
    Placebo tablet
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One K-877 0.05 mg tablet and one placebo tablet were to be taken orally, twice daily in the morning and the evening. Duration of treatment was 12 weeks.

    Arm title
    K-877 0.1 mg twice daily
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    K-877 0.1 mg tablet
    Investigational medicinal product code
    K-877
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One K-877 0.1 mg tablet and one placebo tablet were to be taken orally, twice daily in the morning and the evening. Duration of treatment was 12 weeks.

    Investigational medicinal product name
    Placebo tablet
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One K-877 0.1 mg tablet and one placebo tablet were to be taken orally, twice daily in the morning and the evening. Duration of treatment was 12 weeks.

    Arm title
    K-877 0.2 mg twice daily
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    K-877 0.2 mg tablet
    Investigational medicinal product code
    K-877
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One K-877 0.2 mg tablet and one placebo tablet were to be taken orally, twice daily in the morning and the evening. Duration of treatment was 12 weeks.

    Investigational medicinal product name
    Placebo tablet
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One K-877 0.2 mg tablet and one placebo tablet were to be taken orally, twice daily in the morning and the evening. Duration of treatment was 12 weeks.

    Arm title
    K-877 0.1 mg once daily
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    K-877 0.05 mg tablet
    Investigational medicinal product code
    K-877
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Two K-877 0.05 mg tablets were to be taken orally in the morning and two placebo tablets were to be taken orally in the evening. Duration of treatment was 12 weeks.

    Investigational medicinal product name
    Placebo tablet
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Two K-877 0.05 mg tablets were to be taken orally in the morning and two placebo tablets were to be taken orally in the evening. Duration of treatment was 12 weeks.

    Arm title
    K-877 0.2 mg once daily
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    K-877 0.1 mg tablet
    Investigational medicinal product code
    K-877
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Two K-877 0.1 mg tablets were to be taken orally in the morning and two placebo tablets were to be taken orally in the evening. Duration of treatment was 12 weeks.

    Investigational medicinal product name
    Placebo tablet
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Two K-877 0.1 mg tablets were to be taken orally in the morning and two placebo tablets were to be taken orally in the evening. Duration of treatment was 12 weeks.

    Arm title
    K-877 0.4 mg once daily
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    K-877 0.2 mg tablet
    Investigational medicinal product code
    K-877
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Two K-877 0.2 mg tablets were to be taken orally in the morning and two placebo tablets were to be taken orally in the evening. Duration of treatment was 12 weeks.

    Investigational medicinal product name
    Placebo tablet
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Two K-877 0.2 mg tablets were to be taken orally in the morning and two placebo tablets were to be taken orally in the evening. Duration of treatment was 12 weeks.

    Number of subjects in period 1
    Placebo twice daily K-877 0.05 mg twice daily K-877 0.1 mg twice daily K-877 0.2 mg twice daily K-877 0.1 mg once daily K-877 0.2 mg once daily K-877 0.4 mg once daily
    Started
    60
    58
    58
    57
    58
    58
    59
    Completed
    55
    54
    50
    52
    54
    56
    54
    Not completed
    5
    4
    8
    5
    4
    2
    5
         Protocol deviation
    1
    -
    1
    -
    -
    -
    1
         Adverse event, non-fatal
    1
    -
    2
    3
    2
    1
    1
         Consent withdrawn by subject
    3
    4
    3
    2
    2
    1
    3
         Lost to follow-up
    -
    -
    2
    -
    -
    -
    -

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo twice daily
    Reporting group description
    -

    Reporting group title
    K-877 0.05 mg twice daily
    Reporting group description
    -

    Reporting group title
    K-877 0.1 mg twice daily
    Reporting group description
    -

    Reporting group title
    K-877 0.2 mg twice daily
    Reporting group description
    -

    Reporting group title
    K-877 0.1 mg once daily
    Reporting group description
    -

    Reporting group title
    K-877 0.2 mg once daily
    Reporting group description
    -

    Reporting group title
    K-877 0.4 mg once daily
    Reporting group description
    -

    Reporting group values
    Placebo twice daily K-877 0.05 mg twice daily K-877 0.1 mg twice daily K-877 0.2 mg twice daily K-877 0.1 mg once daily K-877 0.2 mg once daily K-877 0.4 mg once daily Total
    Number of subjects
    60 58 58 57 58 58 59 408
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    38 39 40 37 43 37 39 273
        From 65-84 years
    22 19 18 20 15 21 20 135
        85 years and over
    0 0 0 0 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    61 ± 10.3 59 ± 9.8 58 ± 12.3 61 ± 8.9 57 ± 9.7 59 ± 11.7 59 ± 9.7 -
    Gender categorical
    Units: Subjects
        Female
    17 18 18 17 24 18 14 126
        Male
    43 40 40 40 34 40 45 282

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Placebo twice daily
    Reporting group description
    -

    Reporting group title
    K-877 0.05 mg twice daily
    Reporting group description
    -

    Reporting group title
    K-877 0.1 mg twice daily
    Reporting group description
    -

    Reporting group title
    K-877 0.2 mg twice daily
    Reporting group description
    -

    Reporting group title
    K-877 0.1 mg once daily
    Reporting group description
    -

    Reporting group title
    K-877 0.2 mg once daily
    Reporting group description
    -

    Reporting group title
    K-877 0.4 mg once daily
    Reporting group description
    -

    Primary: Percent change in TG

    Close Top of page
    End point title
    Percent change in TG
    End point description
    End point type
    Primary
    End point timeframe
    Change from baseline to Week 12
    End point values
    Placebo twice daily K-877 0.05 mg twice daily K-877 0.1 mg twice daily K-877 0.2 mg twice daily K-877 0.1 mg once daily K-877 0.2 mg once daily K-877 0.4 mg once daily
    Number of subjects analysed
    55
    52
    50
    49
    50
    52
    52
    Units: percent
        least squares mean (standard error)
    15 ± 4.85
    -21.2 ± 4.96
    -30.8 ± 5.08
    -39.5 ± 5.11
    -19.1 ± 4.98
    -22.7 ± 4.88
    -27.7 ± 4.99
    Statistical analysis title
    Dunnett's Test in MMRM Analysis
    Comparison groups
    Placebo twice daily v K-877 0.05 mg twice daily
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -36.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -53.5
         upper limit
    -18.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.72
    Statistical analysis title
    Dunnett's Test in MMRM Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg twice daily
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -45.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -63.4
         upper limit
    -28.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.81
    Statistical analysis title
    Dunnett's Test in MMRM Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg twice daily
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -54.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -72.1
         upper limit
    -36.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.83
    Statistical analysis title
    Dunnett's Test in MMRM Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg once daily
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -34
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -51.5
         upper limit
    -16.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.76
    Statistical analysis title
    Dunnett's Test in MMRM Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg once daily
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -37.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -55
         upper limit
    -20.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.72
    Statistical analysis title
    Dunnett's Test in MMRM Analysis
    Comparison groups
    Placebo twice daily v K-877 0.4 mg once daily
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -42.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -60.1
         upper limit
    -25.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.75

    Primary: Percent change in non-HDL-C

    Close Top of page
    End point title
    Percent change in non-HDL-C
    End point description
    End point type
    Primary
    End point timeframe
    Change from baseline to Week 12
    End point values
    Placebo twice daily K-877 0.05 mg twice daily K-877 0.1 mg twice daily K-877 0.2 mg twice daily K-877 0.1 mg once daily K-877 0.2 mg once daily K-877 0.4 mg once daily
    Number of subjects analysed
    55
    52
    50
    49
    50
    52
    52
    Units: percent
        least squares mean (standard error)
    2.1 ± 2.9
    -4.8 ± 2.98
    -5.4 ± 3.04
    -6.8 ± 3.05
    -3.2 ± 2.96
    -7.1 ± 2.88
    -5.7 ± 2.99
    Statistical analysis title
    Dunnett's Test in MMRM Analysis
    Comparison groups
    Placebo twice daily v K-877 0.05 mg twice daily
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.307
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -6.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -16.8
         upper limit
    3.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.87
    Statistical analysis title
    Dunnett's Test in MMRM Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg twice daily
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.237
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -7.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -17.5
         upper limit
    2.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.91
    Statistical analysis title
    Dunnett's Test in MMRM Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg twice daily
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.111
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -8.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -19
         upper limit
    1.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.91
    Statistical analysis title
    Dunnett's Test in MMRM Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg once daily
    Number of subjects included in analysis
    105
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.582
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -5.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -15.3
         upper limit
    4.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.88
    Statistical analysis title
    Dunnett's Test in MMRM Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg once daily
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.086
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -9.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -19.1
         upper limit
    0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.85
    Statistical analysis title
    Dunnett's Test in MMRM Analysis
    Comparison groups
    Placebo twice daily v K-877 0.4 mg once daily
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.187
    Method
    Mixed models analysis
    Parameter type
    Mean difference (final values)
    Point estimate
    -7.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -17.8
         upper limit
    2.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.87

    Primary: Percent change in serum creatinine

    Close Top of page
    End point title
    Percent change in serum creatinine
    End point description
    End point type
    Primary
    End point timeframe
    Change from baseline to Week 12
    End point values
    Placebo twice daily K-877 0.05 mg twice daily K-877 0.1 mg twice daily K-877 0.2 mg twice daily K-877 0.1 mg once daily K-877 0.2 mg once daily K-877 0.4 mg once daily
    Number of subjects analysed
    56
    56
    54
    54
    57
    58
    56
    Units: percent
        least squares mean (standard error)
    1.13 ± 1.41
    1.53 ± 1.43
    1.82 ± 1.46
    4.92 ± 1.46
    1.15 ± 1.4
    3.02 ± 1.36
    3.56 ± 1.43
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.05 mg twice daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.824
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.41
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.19
         upper limit
    4.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.83
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg twice daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.706
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.94
         upper limit
    4.34
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.85
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg twice daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.04
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    3.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.17
         upper limit
    7.43
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.85
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg once daily
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.989
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.55
         upper limit
    3.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.82
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg once daily
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.297
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    1.89
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.67
         upper limit
    5.46
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.81
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.4 mg once daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.185
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    2.44
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.17
         upper limit
    6.05
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.84

    Primary: Percent change in Log(Homocysteine)

    Close Top of page
    End point title
    Percent change in Log(Homocysteine)
    End point description
    End point type
    Primary
    End point timeframe
    Change from baseline to Week 12
    End point values
    Placebo twice daily K-877 0.05 mg twice daily K-877 0.1 mg twice daily K-877 0.2 mg twice daily K-877 0.1 mg once daily K-877 0.2 mg once daily K-877 0.4 mg once daily
    Number of subjects analysed
    56
    56
    54
    54
    57
    58
    56
    Units: percent
        least squares mean (standard error)
    3 ± 1.14
    2.9 ± 1.16
    5.89 ± 1.18
    8.45 ± 1.18
    3.93 ± 1.13
    5.91 ± 1.1
    8.37 ± 1.15
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.05 mg twice daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.948
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.01
         upper limit
    2.82
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.48
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg twice daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.054
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    2.89
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.05
         upper limit
    5.82
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.49
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg twice daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    5.45
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.51
         upper limit
    8.39
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.49
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg once daily
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.529
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.93
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.97
         upper limit
    3.82
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.47
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg once daily
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.048
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    2.91
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.03
         upper limit
    5.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.47
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.4 mg once daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    5.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.46
         upper limit
    8.28
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.48

    Secondary: Percent change in HDL-C

    Close Top of page
    End point title
    Percent change in HDL-C
    End point description
    End point type
    Secondary
    End point timeframe
    Change from baseline to Week 12
    End point values
    Placebo twice daily K-877 0.05 mg twice daily K-877 0.1 mg twice daily K-877 0.2 mg twice daily K-877 0.1 mg once daily K-877 0.2 mg once daily K-877 0.4 mg once daily
    Number of subjects analysed
    56
    56
    54
    54
    57
    58
    56
    Units: percent
        least squares mean (standard error)
    -0.05 ± 2.69
    7.59 ± 2.73
    12.84 ± 2.8
    10.89 ± 2.78
    3.66 ± 2.66
    10.32 ± 2.6
    7.29 ± 2.73
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.05 mg twice daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.029
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    7.65
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.77
         upper limit
    14.53
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.5
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg twice daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    12.89
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    5.94
         upper limit
    19.84
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.53
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg twice daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    10.95
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    4.01
         upper limit
    17.88
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.53
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg once daily
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.286
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    3.71
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.12
         upper limit
    10.55
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.48
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg once daily
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    10.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.55
         upper limit
    17.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.47
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.4 mg once daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.036
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    7.35
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.47
         upper limit
    14.22
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.5

    Secondary: Percent change in total cholesterol

    Close Top of page
    End point title
    Percent change in total cholesterol
    End point description
    End point type
    Secondary
    End point timeframe
    Change from baseline to Week 12
    End point values
    Placebo twice daily K-877 0.05 mg twice daily K-877 0.1 mg twice daily K-877 0.2 mg twice daily K-877 0.1 mg once daily K-877 0.2 mg once daily K-877 0.4 mg once daily
    Number of subjects analysed
    56
    56
    54
    54
    57
    58
    56
    Units: percent
        least squares mean (standard error)
    0.65 ± 2.1
    -1.42 ± 2.12
    -1.99 ± 2.17
    -3.13 ± 2.17
    -1.67 ± 2.07
    -2.12 ± 2.02
    -1.68 ± 2.12
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.05 mg twice daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.446
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.08
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.43
         upper limit
    3.28
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.72
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg twice daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.338
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.64
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.05
         upper limit
    2.77
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.75
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg twice daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.169
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -3.78
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.19
         upper limit
    1.62
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.75
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg once daily
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.392
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.32
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.64
         upper limit
    3
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.71
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg once daily
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.306
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.77
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.07
         upper limit
    2.54
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.7
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.4 mg once daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.393
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.33
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.68
         upper limit
    3.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.72

    Secondary: Percent change in Remnant Cholesterol

    Close Top of page
    End point title
    Percent change in Remnant Cholesterol
    End point description
    End point type
    Secondary
    End point timeframe
    Change from baseline to Week 12
    End point values
    Placebo twice daily K-877 0.05 mg twice daily K-877 0.1 mg twice daily K-877 0.2 mg twice daily K-877 0.1 mg once daily K-877 0.2 mg once daily K-877 0.4 mg once daily
    Number of subjects analysed
    56
    56
    54
    54
    57
    58
    56
    Units: percent
        least squares mean (standard error)
    22.25 ± 6.08
    -13.3 ± 6.16
    -26.6 ± 6.3
    -35.8 ± 6.29
    -17.6 ± 6.01
    -23.6 ± 5.87
    -23.2 ± 6.18
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.05 mg twice daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -35.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -51.1
         upper limit
    -20
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.89
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg twice daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -48.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -64.5
         upper limit
    -33.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.98
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg twice daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -58
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -73.7
         upper limit
    -42.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.97
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg once daily
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -39.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -55.3
         upper limit
    -24.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.84
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg once daily
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -45.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -61.2
         upper limit
    -30.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.82
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.4 mg once daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -45.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -61.1
         upper limit
    -29.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.93

    Secondary: Percent change in LDL-C

    Close Top of page
    End point title
    Percent change in LDL-C
    End point description
    End point type
    Secondary
    End point timeframe
    Change from baseline to Week 12
    End point values
    Placebo twice daily K-877 0.05 mg twice daily K-877 0.1 mg twice daily K-877 0.2 mg twice daily K-877 0.1 mg once daily K-877 0.2 mg once daily K-877 0.4 mg once daily
    Number of subjects analysed
    56
    56
    54
    54
    57
    58
    56
    Units: percent
        least squares mean (standard error)
    -3.01 ± 3.56
    5 ± 3.61
    13.06 ± 3.68
    17.49 ± 3.7
    6.18 ± 3.52
    8.21 ± 3.43
    12.65 ± 3.62
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.05 mg twice daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.084
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    8.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.08
         upper limit
    17.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.62
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg twice daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    16.06
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.88
         upper limit
    25.24
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.67
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg twice daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    20.49
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    11.3
         upper limit
    29.68
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.67
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg once daily
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.046
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    9.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.15
         upper limit
    18.22
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.59
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg once daily
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.015
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    11.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.21
         upper limit
    20.22
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.58
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.4 mg once daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    15.66
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.55
         upper limit
    24.77
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.63

    Secondary: Percent change in apolipoprotein A1

    Close Top of page
    End point title
    Percent change in apolipoprotein A1
    End point description
    End point type
    Secondary
    End point timeframe
    Change from baseline to Week 12
    End point values
    Placebo twice daily K-877 0.05 mg twice daily K-877 0.1 mg twice daily K-877 0.2 mg twice daily K-877 0.1 mg once daily K-877 0.2 mg once daily K-877 0.4 mg once daily
    Number of subjects analysed
    56
    56
    54
    52
    57
    57
    56
    Units: percent
        least squares mean (standard error)
    1.82 ± 1.9
    6.25 ± 1.93
    4.78 ± 1.97
    2.23 ± 1.99
    1.72 ± 1.88
    3.71 ± 1.86
    4.47 ± 1.93
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.05 mg twice daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.073
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    4.43
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.42
         upper limit
    9.28
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.47
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg twice daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.234
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    2.97
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.93
         upper limit
    7.86
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.49
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg twice daily
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.871
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    0.41
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.53
         upper limit
    5.35
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.51
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg once daily
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.969
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.92
         upper limit
    4.73
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.45
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg once daily
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.441
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    1.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.94
         upper limit
    6.74
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.46
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.4 mg once daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.284
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    2.65
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.2
         upper limit
    7.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.47

    Secondary: Percent change in apolipoprotein B

    Close Top of page
    End point title
    Percent change in apolipoprotein B
    End point description
    End point type
    Secondary
    End point timeframe
    Change from baseline to Week 12
    End point values
    Placebo twice daily K-877 0.05 mg twice daily K-877 0.1 mg twice daily K-877 0.2 mg twice daily K-877 0.1 mg once daily K-877 0.2 mg once daily K-877 0.4 mg once daily
    Number of subjects analysed
    56
    56
    54
    52
    57
    57
    56
    Units: percent
        least squares mean (standard error)
    0.48 ± 2.94
    2.2 ± 2.99
    -0.23 ± 3.05
    -2.71 ± 3.1
    -1.62 ± 2.91
    -0.57 ± 2.87
    -0.89 ± 2.98
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    K-877 0.05 mg twice daily v Placebo twice daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.653
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    1.72
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.81
         upper limit
    9.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.83
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg twice daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.855
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.71
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.3
         upper limit
    6.89
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.86
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg twice daily
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.415
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -3.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.9
         upper limit
    4.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.91
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg once daily
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.582
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -2.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.57
         upper limit
    5.38
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.8
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg once daily
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.783
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.53
         upper limit
    6.43
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.8
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.4 mg once daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.721
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.9
         upper limit
    6.16
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.83

    Secondary: Percent change in apolipoprotein C3

    Close Top of page
    End point title
    Percent change in apolipoprotein C3
    End point description
    End point type
    Secondary
    End point timeframe
    Change from baseline to Week 12
    End point values
    Placebo twice daily K-877 0.05 mg twice daily K-877 0.1 mg twice daily K-877 0.2 mg twice daily K-877 0.1 mg once daily K-877 0.2 mg once daily K-877 0.4 mg once daily
    Number of subjects analysed
    56
    56
    54
    52
    57
    57
    56
    Units: percent
        least squares mean (standard error)
    5.13 ± 3.85
    -10.3 ± 3.9
    -23.6 ± 3.98
    -30.8 ± 4.04
    -12 ± 3.82
    -19.2 ± 3.75
    -18.6 ± 3.92
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.05 mg twice daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -15.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -25.3
         upper limit
    -5.63
    Variability estimate
    Standard error of the mean
    Dispersion value
    5
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg twice daily
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -28.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -38.6
         upper limit
    -18.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.05
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg twice daily
    Number of subjects included in analysis
    108
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -36
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -46
         upper limit
    -25.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.1
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.1 mg once daily
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -17.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -26.9
         upper limit
    -7.28
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.99
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.2 mg once daily
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -24.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -34.1
         upper limit
    -14.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.97
    Statistical analysis title
    ANCOVA Analysis
    Comparison groups
    Placebo twice daily v K-877 0.4 mg once daily
    Number of subjects included in analysis
    112
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -23.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -33.6
         upper limit
    -13.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.01

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were to be reported from signing of the Informed Consent Form until the last study visit. Serious adverse events were to be collected from signing of the Informed Consent Form until 30 days after the last dose of study medication.
    Adverse event reporting additional description
    Only treatment-emergent adverse events (i.e. events not present prior to the initiation of the study drugs or events already present that worsens in either intensity or frequency following exposure to the study drugs) are summerised here.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.0
    Reporting groups
    Reporting group title
    Placebo twice daily
    Reporting group description
    -

    Reporting group title
    K-877 0.05 mg twice daily
    Reporting group description
    -

    Reporting group title
    K-877 0.1 mg twice daily
    Reporting group description
    -

    Reporting group title
    K-877 0.2 mg twice daily
    Reporting group description
    -

    Reporting group title
    K-877 0.1 mg once daily
    Reporting group description
    -

    Reporting group title
    K-877 0.2 mg once daily
    Reporting group description
    -

    Reporting group title
    K-877 0.4 mg once daily
    Reporting group description
    -

    Serious adverse events
    Placebo twice daily K-877 0.05 mg twice daily K-877 0.1 mg twice daily K-877 0.2 mg twice daily K-877 0.1 mg once daily K-877 0.2 mg once daily K-877 0.4 mg once daily
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 57 (0.00%)
    1 / 58 (1.72%)
    1 / 57 (1.75%)
    3 / 58 (5.17%)
    2 / 58 (3.45%)
    2 / 59 (3.39%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    1 / 57 (1.75%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Laryngeal polyp
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    0 / 57 (0.00%)
    1 / 58 (1.72%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    0 / 57 (0.00%)
    1 / 58 (1.72%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Arrhythmia
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiovascular insufficiency
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    1 / 58 (1.72%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Renal and urinary disorders
    Calculus urinary
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    1 / 58 (1.72%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Drug-induced liver injury
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    0 / 57 (0.00%)
    1 / 58 (1.72%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 57 (0.00%)
    1 / 58 (1.72%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    1 / 59 (1.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Placebo twice daily K-877 0.05 mg twice daily K-877 0.1 mg twice daily K-877 0.2 mg twice daily K-877 0.1 mg once daily K-877 0.2 mg once daily K-877 0.4 mg once daily
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    34 / 60 (56.67%)
    29 / 57 (50.88%)
    21 / 58 (36.21%)
    30 / 57 (52.63%)
    22 / 58 (37.93%)
    29 / 58 (50.00%)
    30 / 59 (50.85%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 57 (0.00%)
    2 / 58 (3.45%)
    4 / 57 (7.02%)
    2 / 58 (3.45%)
    3 / 58 (5.17%)
    1 / 59 (1.69%)
         occurrences all number
    2
    0
    2
    4
    2
    3
    1
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    2 / 60 (3.33%)
    0 / 57 (0.00%)
    1 / 58 (1.72%)
    0 / 57 (0.00%)
    1 / 58 (1.72%)
    4 / 58 (6.90%)
    1 / 59 (1.69%)
         occurrences all number
    2
    0
    1
    0
    1
    4
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    5 / 60 (8.33%)
    1 / 57 (1.75%)
    0 / 58 (0.00%)
    3 / 57 (5.26%)
    0 / 58 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences all number
    5
    1
    0
    3
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 57 (0.00%)
    3 / 58 (5.17%)
    0 / 57 (0.00%)
    1 / 58 (1.72%)
    1 / 58 (1.72%)
    1 / 59 (1.69%)
         occurrences all number
    1
    0
    3
    0
    1
    1
    1
    Back pain
         subjects affected / exposed
    0 / 60 (0.00%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    1 / 57 (1.75%)
    4 / 58 (6.90%)
    0 / 58 (0.00%)
    2 / 59 (3.39%)
         occurrences all number
    0
    0
    0
    1
    4
    0
    2
    Muscle spasms
         subjects affected / exposed
    1 / 60 (1.67%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    3 / 57 (5.26%)
    0 / 58 (0.00%)
    1 / 58 (1.72%)
    1 / 59 (1.69%)
         occurrences all number
    1
    0
    0
    3
    0
    1
    1
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    3 / 60 (5.00%)
    2 / 57 (3.51%)
    1 / 58 (1.72%)
    0 / 57 (0.00%)
    1 / 58 (1.72%)
    3 / 58 (5.17%)
    3 / 59 (5.08%)
         occurrences all number
    3
    2
    1
    0
    1
    3
    3
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    3 / 60 (5.00%)
    1 / 57 (1.75%)
    1 / 58 (1.72%)
    5 / 57 (8.77%)
    2 / 58 (3.45%)
    4 / 58 (6.90%)
    4 / 59 (6.78%)
         occurrences all number
    3
    1
    1
    5
    2
    4
    4
    Urinary tract infection
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 57 (1.75%)
    1 / 58 (1.72%)
    1 / 57 (1.75%)
    2 / 58 (3.45%)
    1 / 58 (1.72%)
    4 / 59 (6.78%)
         occurrences all number
    2
    1
    1
    1
    2
    1
    4
    Influenza
         subjects affected / exposed
    2 / 60 (3.33%)
    1 / 57 (1.75%)
    3 / 58 (5.17%)
    0 / 57 (0.00%)
    0 / 58 (0.00%)
    1 / 58 (1.72%)
    1 / 59 (1.69%)
         occurrences all number
    2
    1
    3
    0
    0
    1
    1

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Oct 2013
    The protocol was amended to modify the followings. - Diaphragm with spermicide as an effective method of contraception for male or female study participants was removed from the inclusion criteria. - The inclusion criteria was added to require male study participants to use a condom with a spermicide during sexual intercourse, from screening to the end of the study, even if their sexual partner is or may be pregnant. - Subgroup analyses and non-compartmental PK analysis methods were added to the statistical analyses.
    18 Mar 2014
    The protocol was amended to allow for the inclusion of subjects who are taking the maximum tolerated dose of statin and still have not reached the LDL-C targets as defined in the protocol.

    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
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA