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    Clinical Trial Results:
    A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Efficacy and Safety Study of Ezetimibe Monotherapy in Children (Ages 6 to 10 Years) With Primary Hypercholesterolemia (Heterozygous Familial and Nonfamilial)

    Summary
    EudraCT number
    		 2008-006271-70
    Trial protocol
    		 NL   FR   IT   GR   Outside EU/EEA  
    Global end of trial date
    13 Apr 2012

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Mar 2016
    First version publication date
    19 Apr 2015
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    P05522
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00867165
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Merck Study Number: MK-0653-170
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000007-PIP01-07
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    13 Apr 2012
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    13 Apr 2012
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Apr 2012
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Determine the effect of ezetimibe 10mg/day compared to placebo on the reduction of low-density lipoprotein cholesterol (LDL-C) from baseline to 12 weeks of treatment in children ≥6 to ≤10 years old with primary hypercholesterolemia (heterozygous familial hypercholesterolemia [HeFH] and nonfamilial).
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    21 May 2009
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 15
    Country: Number of subjects enrolled
    Norway: 8
    Country: Number of subjects enrolled
    France: 5
    Country: Number of subjects enrolled
    Greece: 12
    Country: Number of subjects enrolled
    Italy: 14
    Country: Number of subjects enrolled
    Colombia: 15
    Country: Number of subjects enrolled
    Israel: 4
    Country: Number of subjects enrolled
    Canada: 34
    Country: Number of subjects enrolled
    United States: 31
    Worldwide total number of subjects
    138
    EEA total number of subjects
    54
    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)
    138
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants were to complete a 5-week placebo run-in and a 12-week treatment period

    Pre-assignment
    Screening details
    		 The study enrolled participants 6 to 10 years of age, with a genotype-confirmed or clinical diagnosis of heterozygous familial hypercholesterolemia (HeFH). Other inclusion and exclusion criteria applied.

    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, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ezetimibe
    Arm description
    		 Ezetimibe 10-mg tablet once daily for 12 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ezetimibe
    Investigational medicinal product code
    Other name
    MK-0653, SCH 058235
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    one 10-mg tablet administered once daily during the 12-week double-blind treatment period

    Arm title
    		 Placebo
    Arm description
    		 Placebo to match ezetimibe 10-mg tablet once daily for 12 weeks
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo to match ezetimibe
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered once daily during the 5-week, single-blind, placebo run-in and diet stabilization period and 12-week double-blind treatment period.

    Number of subjects in period 1
    		Ezetimibe Placebo
    Started
    93
    45
    Completed
    89
    45
    Not completed
    4
    0
         Consent withdrawn by subject
    1
    -
         Adverse event, non-fatal
    3
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Ezetimibe
    Reporting group description
    		 Ezetimibe 10-mg tablet once daily for 12 weeks

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo to match ezetimibe 10-mg tablet once daily for 12 weeks

    Reporting group values
    		 Ezetimibe Placebo Total
    Number of subjects
    		 93 45 138
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 8.2 ( 1.7 ) 8.5 ( 1.6 ) -
    Gender categorical
    Units: Subjects
        Female
    		 52 27 79
        Male
    		 41 18 59
    Hypercholesterolemia Stratum
    Units: Subjects
        HeFH
    		 84 41 125
        Non-familial
    		 9 4 13

    End points

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    End points reporting groups
    Reporting group title
    Ezetimibe
    Reporting group description
    		 Ezetimibe 10-mg tablet once daily for 12 weeks

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo to match ezetimibe 10-mg tablet once daily for 12 weeks

    Subject analysis set title
    Ezetimibe 10 mg - Efficacy
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All randomized participants who took at least one dose of study medication and had a baseline value and at least one valid post-baseline evaluation.

    Subject analysis set title
    Placebo - Efficacy
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All randomized participants who took at least one dose of study medication and had a baseline value and at least one valid post-baseline evaluation.

    Primary: Percentage Change from Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12

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    End point title
    		 Percentage Change from Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12
    End point description
    Serum LDL-C levels calculated at baseline and after 12 weeks of study drug administration. LDL-C were calculated by the method of Friedewald equation, LDL-C = Total Cholesterol (TC) – (High-density lipoprotein cholesterol [HDL-C] + triglyceride [TG]/5).
    End point type
    Primary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    85
    42
    Units: Percentage change
        least squares mean (confidence interval 95%)
    -27.7 (-30.8 to -24.59)
    -0.95 (-4.94 to 3.04)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an analysis of covariance (ANCOVA) mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 < 0.001 [2]
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -26.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30.8
         upper limit
    		 -22.69
    Notes
    [1] - Primary hypothesis is that after 12 weeks of treatment, ezetimibe 10 mg/day monotherapy will reduce LDL-C to a greater extent than placebo in children 6 to 10 years old with primary hypercholesterolemia (HeFH and nonfamilial).
    [2] - p-value of <=0.05 for the treatment group comparison was considered supportive of the primary study hypothesis.

    Secondary: Percentage Change from Baseline in Total Cholesterol (TC) at Week 12

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    End point title
    		 Percentage Change from Baseline in Total Cholesterol (TC) at Week 12
    End point description
    Serum TC levels measured using enzymatic methods at baseline and after 12 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    85
    42
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -20.74 (-23.29 to -18.18)
    0.19 (-3.07 to 3.44)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Placebo - Efficacy v Ezetimibe 10 mg - Efficacy
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -20.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.2
         upper limit
    		 -17.65

    Secondary: Percentage Change from Baseline in Apolipoprotein B (Apo B) at Week 12

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    End point title
    		 Percentage Change from Baseline in Apolipoprotein B (Apo B) at Week 12
    End point description
    Serum Apo B measured at baseline and after 12 weeks of study drug administration. Apo B levels were measured at baseline and ONLY at one post-baseline time point; Week 12.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    85
    42
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -21.66 (-24.94 to -18.38)
    -1.42 (-5.55 to 2.7)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline Apo B, treatment, gender, and primary diagnosis.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least Squares Means
    Point estimate
    -20.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.02
         upper limit
    		 -16.45

    Secondary: Percentage Change from Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 12

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    End point title
    		 Percentage Change from Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 12
    End point description
    Serum HDL-C levels measured by photometry after precipitation at baseline and after 12 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    85
    42
    Units: Percentage change
        least squares mean (confidence interval 95%)
    2.11 (-2.27 to 6.48)
    1.41 (-4.14 to 6.96)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.807
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least Squares Means
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.97
         upper limit
    		 6.36

    Secondary: Percentage Change from Baseline in Non-HDL-C at Week 12

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    End point title
    		 Percentage Change from Baseline in Non-HDL-C at Week 12
    End point description
    Serum Non-HDL-C calculated at baseline and after 12 weeks of study drug administration. Non-HDL-C values were calculated as follows: Non-HDL-C (mg/dL) = TC – HDL-C.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    85
    42
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -25.47 (-28.45 to -22.49)
    0.28 (-3.52 to 4.08)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -25.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -29.59
         upper limit
    		 -21.91

    Secondary: Percentage Change from Baseline in Triglycerides (TG) at Week 12

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    End point title
    		 Percentage Change from Baseline in Triglycerides (TG) at Week 12
    End point description
    Serum TG levels measured using enzymatic methods at baseline and after 12 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    85
    42
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -6.23 (-12.73 to 0.75)
    8.44 (-2.03 to 20.03)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis was based on log-transformed data using a constrained longitudinal data analysis (cLDA) model with terms for treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and the interaction of treatment by study week. The difference in Least-Square (LS) Means was based on the difference in the back transformed model-based LS means and the associated confidence interval is calculated using the Delta method.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.021
    Method
    		 constrained longitudinal data analysis
    Parameter type
    		 Difference in Least Squares Means
    Point estimate
    -14.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.35
         upper limit
    		 -2

    Secondary: Percentage Change From Baseline in LDL-C at Week 2

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    End point title
    		 Percentage Change From Baseline in LDL-C at Week 2
    End point description
    Serum LDL-C levels calculated at baseline and after 2 weeks of study drug administration. LDL-C were calculated by the method of Friedewald equation, LDL-C = Total Cholesterol (TC) – (High-density lipoprotein cholesterol [HDL-C] + triglyceride [TG]/5).
    End point type
    Secondary
    End point timeframe
    Baseline and Week 2
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    91
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -24.75 (-27.8 to -21.69)
    0.23 (-3.74 to 4.2)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Mean
    Point estimate
    -24.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.95
         upper limit
    		 -20.99

    Secondary: Percentage Change From Baseline in LDL-C at Week 4

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    End point title
    		 Percentage Change From Baseline in LDL-C at Week 4
    End point description
    Serum LDL-C levels calculated at baseline and after 4 weeks of study drug administration. LDL-C were calculated by the method of Friedewald equation, LDL-C = Total Cholesterol (TC) – (High-density lipoprotein cholesterol [HDL-C] + triglyceride [TG]/5).
    End point type
    Secondary
    End point timeframe
    Baseline and Week 4
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    90
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -26.93 (-29.81 to -24.05)
    -2.99 (-6.66 to 0.68)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -23.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.49
         upper limit
    		 -20.39

    Secondary: Percentage Change From Baseline in LDL-C at Week 8

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    End point title
    		 Percentage Change From Baseline in LDL-C at Week 8
    End point description
    Serum LDL-C levels calculated at baseline and after 8 weeks of study drug administration. LDL-C were calculated by the method of Friedewald equation, LDL-C = Total Cholesterol (TC) – (High-density lipoprotein cholesterol [HDL-C] + triglyceride [TG]/5).
    End point type
    Secondary
    End point timeframe
    Baseline and Week 8
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    90
    44
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -27.22 (-30.3 to -24.15)
    0.49 (-3.46 to 4.43)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -27.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -31.7
         upper limit
    		 -23.73

    Secondary: Percentage Change from Baseline in TC at Week 2

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    End point title
    		 Percentage Change from Baseline in TC at Week 2
    End point description
    Serum TC levels measured using enzymatic methods at baseline and after 2 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 2
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    91
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -18.69 (-21.21 to -16.18)
    1.4 (-1.83 to 4.63)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -20.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.3
         upper limit
    		 -16.89

    Secondary: Percentage Change From Baseline in TC at Week 4

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    End point title
    		 Percentage Change From Baseline in TC at Week 4
    End point description
    Serum TC levels measured using enzymatic methods at baseline and after 4 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 4
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    90
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -20.57 (-23.05 to -18.08)
    -0.29 (-3.45 to 2.86)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -20.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.39
         upper limit
    		 -17.15

    Secondary: Percentage Change From Baseline in TC at Week 8

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    End point title
    		 Percentage Change From Baseline in TC at Week 8
    End point description
    Serum TC levels measured using enzymatic methods at baseline and after 8 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 8
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    90
    44
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -20.84 (-23.4 to -18.27)
    0.54 (-2.73 to 3.81)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -21.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.67
         upper limit
    		 -18.08

    Secondary: Percentage Change From Baseline in HDL-C at Week 2

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    End point title
    		 Percentage Change From Baseline in HDL-C at Week 2
    End point description
    Serum HDL-C levels measured by photometry after precipitation at baseline and after 2 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 2
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    91
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    0.01 (-4.28 to 4.3)
    0.96 (-4.51 to 6.43)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.733
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.46
         upper limit
    		 4.55

    Secondary: Percentage Change From Baseline in HDL-C at Week 4

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    End point title
    		 Percentage Change From Baseline in HDL-C at Week 4
    End point description
    Serum HDL-C levels measured by photometry after precipitation at baseline and after 4 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 4
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    90
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    0.86 (-3.69 to 5.42)
    0.33 (-5.54 to 6.19)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.863
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    0.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.59
         upper limit
    		 6.66

    Secondary: Percentage Change From Baseline in HDL-C at Week 8

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    End point title
    		 Percentage Change From Baseline in HDL-C at Week 8
    End point description
    Serum HDL-C levels measured by photometry after precipitation at baseline and after 8 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 8
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    90
    44
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    1.41 (-2.95 to 5.77)
    -0.52 (-6.04 to 5)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Placebo - Efficacy v Ezetimibe 10 mg - Efficacy
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.501
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    1.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.71
         upper limit
    		 7.56

    Secondary: Percentage Change From Baseline in Non-HDL-C at Week 2

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    End point title
    		 Percentage Change From Baseline in Non-HDL-C at Week 2
    End point description
    Serum Non-HDL-C calculated at baseline and after 2 weeks of study drug administration. Non-HDL-C values were calculated as follows: Non-HDL-C (mg/dL) = TC – HDL-C.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 2
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    91
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -22.54 (-25.41 to -19.67)
    1.64 (-2.03 to 5.3)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -24.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.78
         upper limit
    		 -20.58

    Secondary: Percentage Change From Baseline in Non-HDL-C at Week 4

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    End point title
    		 Percentage Change From Baseline in Non-HDL-C at Week 4
    End point description
    Serum Non-HDL-C calculated at baseline and after 4 weeks of study drug administration. Non-HDL-C values were calculated as follows: Non-HDL-C (mg/dL) = TC – HDL-C.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 4
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    90
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -24.94 (-27.75 to -22.14)
    -0.33 (-3.88 to 3.22)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -24.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.06
         upper limit
    		 -21.16

    Secondary: Percentage Change From Baseline in Non-HDL-C at Week 8

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    End point title
    		 Percentage Change From Baseline in Non-HDL-C at Week 8
    End point description
    Serum Non-HDL-C calculated at baseline and after 8 weeks of study drug administration. Non-HDL-C values were calculated as follows: Non-HDL-C (mg/dL) = TC – HDL-C.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 8
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    90
    44
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -25.41 (-28.37 to -22.45)
    1.14 (-2.63 to 4.92)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Placebo - Efficacy v Ezetimibe 10 mg - Efficacy
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -26.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30.35
         upper limit
    		 -22.75

    Secondary: Percentage Change From Baseline in TG at Week 2

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    End point title
    		 Percentage Change From Baseline in TG at Week 2
    End point description
    Serum TG levels measured using enzymatic methods at baseline and after 2 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 2
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    91
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -3.9 (-10.66 to 3.37)
    5.83 (-4.76 to 17.59)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis was based on log-transformed data using a cLDA model with terms for treatment, gender, primary diagnosis, study week, and the interaction of treatment by study week. The difference in LS Means was based on the difference in the back transformed model-based LS means and the associated confidence interval is calculated using the Delta method.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.137
    Method
    		 Constrained longitudinal data analysis
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -9.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.73
         upper limit
    		 3.27

    Secondary: Percentage Change From Baseline in TG at Week 4

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    End point title
    		 Percentage Change From Baseline in TG at Week 4
    End point description
    Serum TG levels measured using enzymatic methods at baseline and after 4 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 4
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    90
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -5.54 (-11.05 to 0.31)
    9.65 (0.6 to 19.53)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis was based on log-transformed data using a cLDA model with terms for treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and the interaction of treatment by study week. The difference in LS Means was based on the difference in the back transformed model-based LS means and the associated confidence interval is calculated using the Delta method.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.005
    Method
    		 Constrained longitudinal data analysis
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -15.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.05
         upper limit
    		 -4.34

    Secondary: Percentage Change From Baseline in TG at Week 8

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    End point title
    		 Percentage Change From Baseline in TG at Week 8
    End point description
    Serum TG levels measured using enzymatic methods at baseline and after 8 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 8
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    90
    44
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -9.99 (-16.28 to -3.21)
    -1.38 (-11.02 to 9.31)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis was based on log-transformed data using a cLDA model with terms for treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and the interaction of treatment by study week. The difference in LS Means was based on the difference in the back transformed model-based LS means and the associated confidence interval is calculated using the Delta method.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.149
    Method
    		 Constrained longitudinal data analysis
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -8.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.44
         upper limit
    		 3.23

    Secondary: Percentage Change from Baseline in Apolipoprotein A-I (Apo A-I) at Week 12

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    End point title
    		 Percentage Change from Baseline in Apolipoprotein A-I (Apo A-I) at Week 12
    End point description
    Serum Apo A-I levels measured at baseline and after 12 weeks of study drug administration. Apo A-I levels were measured at baseline and ONLY at one post-baseline time point; Week 12.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    85
    42
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    1.8 (-1.86 to 5.46)
    3.71 (-0.87 to 8.3)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline Apo A-I, treatment, gender, and primary diagnosis.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.373
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -1.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.15
         upper limit
    		 2.32

    Secondary: Percentage Change from Baseline in TC:HDL-C Ratio at Week 2

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    End point title
    		 Percentage Change from Baseline in TC:HDL-C Ratio at Week 2
    End point description
    Serum TC:HDL-C Ratio calculated at baseline and after 2 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 2
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    91
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -17.21 (-21.08 to -13.34)
    2.56 (-2.37 to 7.48)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -19.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.7
         upper limit
    		 -14.82

    Secondary: Percentage Change From Baseline in TC:HDL-C Ratio at Week 4

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    End point title
    		 Percentage Change From Baseline in TC:HDL-C Ratio at Week 4
    End point description
    Serum TC:HDL-C Ratio calculated at baseline and after 4 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 4
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    90
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -19.36 (-23.16 to -15.56)
    1.48 (-3.3 to 6.25)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -20.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25.59
         upper limit
    		 -16.07

    Secondary: Percentage Change From Baseline in TC:HDL-C Ratio at Week 8

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    End point title
    		 Percentage Change From Baseline in TC:HDL-C Ratio at Week 8
    End point description
    Serum TC:HDL-C Ratio calculated at baseline and after 8 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 8
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    90
    44
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -20.07 (-24.2 to -15.94)
    3.41 (-1.87 to 8.7)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for treatment, baseline covariate corresponding to the analysis parameter, gender, primary diagnosis, study week and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -23.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -29
         upper limit
    		 -17.97

    Secondary: Percentage Change From Baseline in TC:HDL-C Ratio at Week 12

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    End point title
    		 Percentage Change From Baseline in TC:HDL-C Ratio at Week 12
    End point description
    Serum TC:HDL-C Ratio calculated at baseline and after 12 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    85
    42
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -21.09 (-24.98 to -17.19)
    1.2 (-3.7 to 6.11)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -22.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.25
         upper limit
    		 -17.34

    Secondary: Percentage Change From Baseline in LDL-C:HDL-C Ratio at Week 2

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    End point title
    		 Percentage Change From Baseline in LDL-C:HDL-C Ratio at Week 2
    End point description
    Serum LDL-C:HDL-C Ratio calculated at baseline and after 2 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 2
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    91
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -23.35 (-27.69 to -19.01)
    1.15 (-4.35 to 6.65)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -24.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -29.88
         upper limit
    		 -19.12

    Secondary: Percentage Change From Baseline in LDL-C:HDL-C Ratio at Week 4

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    End point title
    		 Percentage Change From Baseline in LDL-C:HDL-C Ratio at Week 4
    End point description
    Serum LDL-C:HDL-C Ratio calculated at baseline and after 4 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 4
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    90
    42
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -25.72 (-30.12 to -21.33)
    -0.57 (-6.14 to 5)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -25.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30.69
         upper limit
    		 -19.62

    Secondary: Percentage Change From Baseline in LDL-C:HDL-C Ratio at Week 8

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    End point title
    		 Percentage Change From Baseline in LDL-C:HDL-C Ratio at Week 8
    End point description
    Serum LDL-C:HDL-C Ratio calculated at baseline and after 8 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 8
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    90
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -26.43 (-31.21 to -21.66)
    2.87 (-3.28 to 9.02)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -29.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -35.71
         upper limit
    		 -22.91

    Secondary: Percentage Change From Baseline in LDL-C:HDL-C Ratio at Week 12

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    End point title
    		 Percentage Change From Baseline in LDL-C:HDL-C Ratio at Week 12
    End point description
    Serum LDL-C:HDL-C Ratio calculated at baseline and after 12 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    85
    42
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -28.01 (-32.65 to -23.36)
    0.34 (-5.57 to 6.25)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Mean
    Point estimate
    -28.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -34.41
         upper limit
    		 -22.29

    Secondary: Percentage Change From Baseline in Apo B:Apo A-I Ratio at Week 12

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    End point title
    		 Percentage Change From Baseline in Apo B:Apo A-I Ratio at Week 12
    End point description
    Serum Apo B:Apo A-I Ratio calculated at baseline and after 12 weeks of study drug administration
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    85
    42
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -22.16 (-26.13 to -18.19)
    -2.87 (-7.84 to 2.09)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline Apo B:Apo A-I ratio, treatment, gender, and primary diagnosis.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -19.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.87
         upper limit
    		 -14.7

    Secondary: Percentage Change from Baseline in High-sensitivity C-reactive protein (hs-CRP) at Week 4

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    End point title
    		 Percentage Change from Baseline in High-sensitivity C-reactive protein (hs-CRP) at Week 4
    End point description
    Plasma hs-CRP measured at baseline and after 4 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 4
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    90
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    10 (-15.65 to 43.45)
    56.11 (7.68 to 126.32)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis was based on log-transformed data using a cLDA model with terms for treatment, gender, primary diagnosis (HeFH, Non-familial), study week (4 and 12), and the interaction of treatment by study week. The difference in LS Means was based on the difference in the back transformed model-based LS means and the associated confidence interval is calculated using the Delta method.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.116
    Method
    		 Constrained longitudinal data analysis
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -46.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -108.14
         upper limit
    		 15.92

    Secondary: Percentage Change from Baseline in High-sensitivity C-reactive protein (hs-CRP) at Week 12

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    End point title
    		 Percentage Change from Baseline in High-sensitivity C-reactive protein (hs-CRP) at Week 12
    End point description
    Plasma hs-CRP measured at baseline and after 12 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    85
    42
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    9.35 (-13.47 to 38.19)
    -7.92 (-33.48 to 27.46)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis was based on log-transformed data using a cLDA model with terms for treatment, gender, primary diagnosis (HeFH, Non-familial), study week (4 and 12), and the interaction of treatment by study week. The difference in LS Means was based on the difference in the back transformed model-based LS means and the associated confidence interval is calculated using the Delta method.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.382
    Method
    		 Constrained longitudinal data analysis
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    17.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.46
         upper limit
    		 55

    Secondary: Percent Change From Baseline in Sitosterol at Week 2

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    End point title
    		 Percent Change From Baseline in Sitosterol at Week 2
    End point description
    Plasma sitosterol measured at baseline and after 2 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 2
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    89
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -50.2 (-54.65 to -45.76)
    -0.59 (-6.26 to 5.08)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -49.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -55.36
         upper limit
    		 -43.87

    Secondary: Percentage Change From Baseline in Sitosterol at Week 4

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    End point title
    		 Percentage Change From Baseline in Sitosterol at Week 4
    End point description
    Plasma sitosterol measured at baseline and after 4 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 4
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    87
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -58.82 (-63.04 to -54.61)
    -0.3 (-5.52 to 4.93)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    130
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -58.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -63.67
         upper limit
    		 -53.38

    Secondary: Percentage Change From Baseline in Sitosterol at Week 8

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    End point title
    		 Percentage Change From Baseline in Sitosterol at Week 8
    End point description
    Plasma sitosterol measured at baseline and after 8 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 8
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    86
    44
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -61.59 (-66.39 to -56.78)
    -0.57 (-6.69 to 5.56)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    130
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -61.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -67.51
         upper limit
    		 -54.53

    Secondary: Percentage Change From Baseline in Sitosterol at Week 12

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    End point title
    		 Percentage Change From Baseline in Sitosterol at Week 12
    End point description
    Plasma sitosterol measured at baseline and after 12 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    82
    41
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -60.65 (-67.39 to -53.92)
    2.09 (-7.01 to 11.18)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    123
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -62.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -73.22
         upper limit
    		 -52.26

    Secondary: Percentage Change From Baseline in Campesterol at Week 2

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    End point title
    		 Percentage Change From Baseline in Campesterol at Week 2
    End point description
    Plasma campesterol measured at baseline and after 2 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 2
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    89
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -53.87 (-57.99 to -49.74)
    -4.38 (-9.66 to 0.9)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -49.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -54.83
         upper limit
    		 -44.14

    Secondary: Percentage Change From Baseline in Campesterol at Week 4

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    End point title
    		 Percentage Change From Baseline in Campesterol at Week 4
    End point description
    Plasma campesterol measured at baseline and after 4 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 4
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    87
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -62.27 (-66.21 to -58.32)
    -4.28 (-9.2 to 0.65)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    130
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -57.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -62.87
         upper limit
    		 -53.11

    Secondary: Percentage Change From Baseline in Campesterol at Week 8

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    End point title
    		 Percentage Change From Baseline in Campesterol at Week 8
    End point description
    Plasma campesterol measured at baseline and after 8 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 8
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    86
    44
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -66.79 (-71.21 to -62.37)
    -4.19 (-9.83 to 1.45)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    130
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -62.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -68.54
         upper limit
    		 -56.66

    Secondary: Percentage Change From Baseline in Campesterol at Week 12

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    End point title
    		 Percentage Change From Baseline in Campesterol at Week 12
    End point description
    Plasma campesterol measured at baseline and after 12 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    82
    41
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -67.59 (-73.68 to -61.5)
    -2.92 (-11.15 to 5.31)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    123
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -64.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -74.11
         upper limit
    		 -55.23

    Secondary: Percentage Change From Baseline in Cholestanol at Week 2

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    End point title
    		 Percentage Change From Baseline in Cholestanol at Week 2
    End point description
    Plasma cholestanol measured at baseline and after 2 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 2
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    89
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -25.44 (-30.3 to -20.59)
    -7.09 (-13.29 to -0.9)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Placebo - Efficacy v Ezetimibe 10 mg - Efficacy
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -18.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.7
         upper limit
    		 -11.99

    Secondary: Percentage Change From Baseline in Cholestanol at Week 4

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    End point title
    		 Percentage Change From Baseline in Cholestanol at Week 4
    End point description
    Plasma cholestanol measured at baseline and after 4 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 4
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    87
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -27.4 (-31.95 to -22.85)
    -1.79 (-7.42 to 3.85)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    130
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -25.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -31.2
         upper limit
    		 -20.02

    Secondary: Percentage Change From Baseline in Cholestanol at Week 8

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    End point title
    		 Percentage Change From Baseline in Cholestanol at Week 8
    End point description
    Plasma cholestanol measured at baseline and after 8 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 8
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    86
    44
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -29.19 (-33.98 to -24.39)
    -0.44 (-6.44 to 5.56)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    130
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -28.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -34.89
         upper limit
    		 -22.59

    Secondary: Percentage Change From Baseline in Cholestanol at Week 12

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    End point title
    		 Percentage Change From Baseline in Cholestanol at Week 12
    End point description
    Plasma cholestanol measured at baseline and after 12 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    82
    41
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    -28.71 (-34.44 to -22.99)
    3.42 (-4.07 to 10.92)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    123
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    -32.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -40.38
         upper limit
    		 -23.9

    Secondary: Percentage Change From Baseline in Lathosterol at Week 2

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    End point title
    		 Percentage Change From Baseline in Lathosterol at Week 2
    End point description
    Plasma lathosterol measured at baseline and after 2 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 2
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    89
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    34.07 (24.68 to 43.45)
    14.06 (2.22 to 25.9)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Mean
    Point estimate
    20.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.1
         upper limit
    		 31.91

    Secondary: Percentage Change From Baseline in Lathosterol at Week 4

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    End point title
    		 Percentage Change From Baseline in Lathosterol at Week 4
    End point description
    Plasma lathosterol measured at baseline and after 4 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 4
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    87
    43
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    33.02 (23.44 to 42.6)
    6.73 (-5.27 to 18.73)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    130
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    26.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 13.99
         upper limit
    		 38.58

    Secondary: Percentage Change From Baseline in Lathosterol at Week 8

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    End point title
    		 Percentage Change From Baseline in Lathosterol at Week 8
    End point description
    Plasma lathosterol measured at baseline and after 8 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 8
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    86
    44
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    35.87 (26.14 to 45.61)
    -0.82 (-12.99 to 11.34)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for treatment, baseline covariate corresponding to the analysis parameter, gender, primary diagnosis, study week and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    130
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Mean
    Point estimate
    36.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 24.12
         upper limit
    		 49.28

    Secondary: Percentage Change From Baseline in Lathosterol at Week 12

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    End point title
    		 Percentage Change From Baseline in Lathosterol at Week 12
    End point description
    Plasma lathosterol measured at baseline and after 12 weeks of study drug administration.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Ezetimibe 10 mg - Efficacy Placebo - Efficacy
    Number of subjects analysed
    82
    41
    Units: Percentage Change
        least squares mean (confidence interval 95%)
    36.62 (26.46 to 46.78)
    12.57 (-0.36 to 25.5)
    Statistical analysis title
    		 Comparison of Percentage Change from Baseline
    Statistical analysis description
    Analysis performed using an ANCOVA mixed model with fixed effects for baseline covariate corresponding to the analysis parameter, treatment, gender, primary diagnosis (HeFH, Non-familial), study week (2, 4, 8, 12), and treatment by study week interaction.
    Comparison groups
    Ezetimibe 10 mg - Efficacy v Placebo - Efficacy
    Number of subjects included in analysis
    123
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least-Squares Means
    Point estimate
    24.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.43
         upper limit
    		 37.67

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 12 weeks
    Adverse event reporting additional description
    All-Patients-as-Treated (APaT) Population defined as all randomized participants who received at least one dose of double-blind study therapy.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    15.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    Ezetimibe 10 mg
    Reporting group description
    		 -

    Serious adverse events
    		 Placebo Ezetimibe 10 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 92 (2.17%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Congenital, familial and genetic disorders
    Epilepsy Congenital
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 92 (1.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 92 (1.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Ezetimibe 10 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    18 / 45 (40.00%)
    27 / 92 (29.35%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    6 / 45 (13.33%)
    4 / 92 (4.35%)
         occurrences all number
    6
    9
    Gastrointestinal disorders
    Abdominal Pain
         subjects affected / exposed
    5 / 45 (11.11%)
    4 / 92 (4.35%)
         occurrences all number
    6
    4
    Diarrhoea
         subjects affected / exposed
    4 / 45 (8.89%)
    1 / 92 (1.09%)
         occurrences all number
    5
    2
    Nausea
         subjects affected / exposed
    3 / 45 (6.67%)
    1 / 92 (1.09%)
         occurrences all number
    3
    1
    Vomiting
         subjects affected / exposed
    3 / 45 (6.67%)
    2 / 92 (2.17%)
         occurrences all number
    3
    2
    Infections and infestations
    Influenza
         subjects affected / exposed
    3 / 45 (6.67%)
    5 / 92 (5.43%)
         occurrences all number
    3
    5
    Nasopharyngitis
         subjects affected / exposed
    5 / 45 (11.11%)
    10 / 92 (10.87%)
         occurrences all number
    5
    10
    Upper Respiratory Tract Infection
         subjects affected / exposed
    1 / 45 (2.22%)
    7 / 92 (7.61%)
         occurrences all number
    1
    7

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

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

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