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    Clinical Trial Results:
    A 1-Year, Worldwide, Multicenter, Double-Blind, Randomized, Parallel, Placebo-Controlled Study to Assess the Efficacy and Tolerability of Anacetrapib When Added to Ongoing Statin Therapy With or Without Other Lipid Modifying Medication(s) in Patients with Heterozygous Familial Hypercholesterolemia

    Summary
    EudraCT number
    		 2011-004525-27
    Trial protocol
    		 GB   DE   NL   ES   CZ  
    Global end of trial date
    13 Nov 2018

    Results information
    Results version number
    		 v2(current)
    This version publication date
    17 Nov 2019
    First version publication date
    19 Jul 2015
    Other versions
    		 v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    0859-020
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01524289
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, 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)
    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
    13 Nov 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    12 Feb 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Nov 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objective of this study is to evaluate the efficacy and tolerability of adding anacetrapib to ongoing statin therapy in participants with heterozygous familial hypercholesterolemia (HeFH).
    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
    03 Feb 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 5 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 102
    Country: Number of subjects enrolled
    Norway: 29
    Country: Number of subjects enrolled
    Spain: 48
    Country: Number of subjects enrolled
    United Kingdom: 25
    Country: Number of subjects enrolled
    France: 20
    Country: Number of subjects enrolled
    Germany: 15
    Country: Number of subjects enrolled
    Canada: 50
    Country: Number of subjects enrolled
    Russian Federation: 8
    Country: Number of subjects enrolled
    United States: 9
    Worldwide total number of subjects
    306
    EEA total number of subjects
    239
    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)
    239
    From 65 to 84 years
    67
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted at 26 study centers. Participants were to complete a 2-week placebo run-in period, a 52-week randomized treatment phase and a 12-week reversal phase (safety follow-up).

    Pre-assignment
    Screening details
    		 The study enrolled participants who were 18 to 80 years old, had a genotype-confirmed or clinical diagnosis of heterozygous familial hypercholesterolemia (HeFH), and had been treated with an optimal dose of statin for at least 6 weeks.

    Period 1
    Period 1 title
    Overall Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Anacetrapib 100 mg
    Arm description
    		 Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Anacetrapib
    Investigational medicinal product code
    Other name
    MK-0859
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One 100 mg tablet once daily for 52 weeks

    Arm title
    		 Placebo
    Arm description
    		 Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo to match anacetrapib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    one placebo tablet once daily for 52 weeks

    Number of subjects in period 1
    		Anacetrapib 100 mg Placebo
    Started
    204
    102
    Treated
    203
    102
    Completed
    174
    88
    Not completed
    30
    14
         Physician decision
    1
    -
         Did not take study medication
    1
    -
         Adverse event, non-fatal
    12
    5
         Withdrawal by Subject
    11
    7
         Lost to follow-up
    -
    1
         Protocol deviation
    5
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Anacetrapib 100 mg
    Reporting group description
    		 Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.

    Reporting group values
    		 Anacetrapib 100 mg Placebo Total
    Number of subjects
    		 204 102 306
    Age Categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 55.0 ( 11.8 ) 55.7 ( 11.9 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 84 52 136
        Male
    		 120 50 170
    Race/Ethnicity
    Units: Subjects
        Asian
    		 2 0 2
        Black or African American
    		 0 1 1
        Multi-racial
    		 3 1 4
        White
    		 199 100 299

    End points

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    End points reporting groups
    Reporting group title
    Anacetrapib 100 mg
    Reporting group description
    		 Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks during the treatment phase.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks during the treatment phase.

    Primary: Percent Change from Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) - Treatment Phase

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    End point title
    		 Percent Change from Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) - Treatment Phase
    End point description
    LDL-C levels were measured at baseline and week 52 (or at discontinuation) using a beta quantification method. The Treatment Phase was the period from the date of the participant’s first dose of study treatment (randomization visit, Visit 3) to the participant's last visit on treatment (discontinuation visit or Visit 8 [Week 52]). The full analysis set (FAS) population consisted of all randomized participants who received at least one dose of study treatment, had at least one post randomization observation for the analysis endpoint subsequent to at least one dose of study treatment and had baseline data for those analyses that require baseline data.
    End point type
    Primary
    End point timeframe
    Baseline and Week 52
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    165
    85
    Units: Percent Change
        least squares mean (confidence interval 95%)
    -36.0 (-39.5 to -32.5)
    3.7 (-1.2 to 8.6)
    Statistical analysis title
    		 Superiority
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    250
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in Least Squares (LS) Means
    Point estimate
    -39.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -45.7
         upper limit
    		 -33.7

    Primary: Percentage of Participants with Any Adverse Event - Treatment Phase

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    End point title
    		 Percentage of Participants with Any Adverse Event - Treatment Phase
    End point description
    An adverse event (AE) or experience was any unfavorable and unintended change in the structure (signs), function (symptoms), or chemistry (laboratory data) of the body temporally associated with any use of a study treatment, whether or not considered related to the use of the study treatment. Any worsening of a preexisting condition which was temporally associated with the use of the study treatment is also an AE. The percentage of participants with any adverse event during the treatment phase is presented.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    203
    102
    Units: Percentage of Participants
        number (not applicable)
    76.4
    78.4
    Statistical analysis title
    		 Adverse Events: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    305
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in Percentages
    Point estimate
    -2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.5
         upper limit
    		 8.4

    Primary: Percentage of Participants with Any Treatment-Related Adverse Event - Treatment Phase

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    End point title
    		 Percentage of Participants with Any Treatment-Related Adverse Event - Treatment Phase
    End point description
    An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of the treatment. Any worsening of a preexisting condition which was temporally associated with the use of the study treatment was also an AE. AEs reported by the investigator as definitely, probably or possibly related to study treatment were considered treatment-related. The percentage of participants with any treatment-related adverse event during the treatment phase is presented. The APaT population consisted of all randomized participants who received at least one dose of study treatment.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    203
    102
    Units: Percentage of Participants
        number (not applicable)
    18.2
    13.7
    Statistical analysis title
    		 Treatment AE: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    305
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in Percentages
    Point estimate
    4.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.8
         upper limit
    		 12.6

    Primary: Percentage of Participants with Any Serious Adverse Event - Treatment Phase

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    End point title
    		 Percentage of Participants with Any Serious Adverse Event - Treatment Phase
    End point description
    A serious adverse experience (SAE) was any adverse event that occurred at any dose that resulted in death or was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, or was a congenital anomaly/birth defect. The percentage of participants with any serious adverse event during the treatment phase is presented. The APaT population consisted of all randomized participants who received at least one dose of study treatment.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    203
    102
    Units: Percentage of Participants
        number (not applicable)
    8.9
    9.8
    Statistical analysis title
    		 SAEs: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    305
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in Percentages
    Point estimate
    -0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.9
         upper limit
    		 5.6

    Primary: Percentage of Participants Discontinuing Study Treatment Due to an Adverse Event - Treatment Phase

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    End point title
    		 Percentage of Participants Discontinuing Study Treatment Due to an Adverse Event - Treatment Phase
    End point description
    An adverse event (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of the drug. Any worsening of a preexisting condition which was temporally associated with the use of the study drug was also an AE. The percentage of participants who discontinued study treatment due to an AE during the treatment phase is presented. The APaT population consists of all randomized participants who received at least one dose of study treatment.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    203
    102
    Units: Percentage of Participants
        number (not applicable)
    5.9
    4.9
    Statistical analysis title
    		 Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    305
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.168
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in Percentages
    Point estimate
    -8.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.1
         upper limit
    		 3.5

    Primary: Percentage of Participants with Changes in Systolic Blood Pressure (SBP) >= 10 mm Hg

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    End point title
    		 Percentage of Participants with Changes in Systolic Blood Pressure (SBP) >= 10 mm Hg
    End point description
    Participants had SBP assessed at baseline and throughout the 52-week treatment period. Percentage of participants who had a SBP reading that was >= 10 mm Hg higher than their baseline SBP for any assessment performed during the treatment phase is presented. The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    202
    101
    Units: Percentage of Participants
        number (not applicable)
    45.0
    53.5
    Statistical analysis title
    		 SBP >= 10: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    303
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.168
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in Percentages
    Point estimate
    -8.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.1
         upper limit
    		 3.5

    Primary: Percentage of Participants with Changes in SBP >= 15 mm Hg

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    End point title
    		 Percentage of Participants with Changes in SBP >= 15 mm Hg
    End point description
    Participants had SBP assessed at baseline and throughout the 52-week treatment period. The percentage of participants who had a SBP reading that was >= 15 mm Hg higher than their baseline SBP for any assessment performed during the treatment phase is presented. The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    202
    101
    Units: Percentage of Participants
        number (not applicable)
    26.2
    33.7
    Statistical analysis title
    		 SBP >= 15: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    303
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.179
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in Percentages
    Point estimate
    -7.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.7
         upper limit
    		 3.3

    Primary: Percentage of Participants with Changes in Diastolic Blood Pressure (DBP) >= 10 mm Hg

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    End point title
    		 Percentage of Participants with Changes in Diastolic Blood Pressure (DBP) >= 10 mm Hg
    End point description
    Participants had DBP assessed at baseline and throughout the 52-week treatment period. The percentage of participants who had a DBP reading that was >= 10 mm Hg higher than their baseline DBP for any assessment performed during the treatment phase is presented. The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    202
    101
    Units: Percentage of Participants
        number (not applicable)
    22.8
    36.6
    Statistical analysis title
    		 DBP >= 10: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    303
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.011
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in Percentages
    Point estimate
    -13.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25
         upper limit
    		 -3.1

    Primary: Percentage of Participants with Sodium Levels > Upper Limit of Normal (ULN)

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    End point title
    		 Percentage of Participants with Sodium Levels > Upper Limit of Normal (ULN)
    End point description
    Participants had sodium levels assessed throughout the 52-week treatment period. The percentage of participants who had any sodium level that was greater than the ULN of 145 mEq/L during the treatment phase is presented. The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    202
    101
    Units: Percentage of Participants
        number (not applicable)
    11.4
    9.9
    Statistical analysis title
    		 Sodium > ULN: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    303
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.696
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in Percentages
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.8
         upper limit
    		 8.4

    Primary: Percentage of Participants with Chloride Levels > ULN

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    End point title
    		 Percentage of Participants with Chloride Levels > ULN
    End point description
    Participants had chloride levels assessed throughout the 52-week treatment period. The percentage of participants who had any chloride level that was > the ULN of 110 mEq/L during the treatment phase is presented. The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    202
    101
    Units: Percentage of Participants
        number (not applicable)
    0.5
    0.0
    Statistical analysis title
    		 Chloride > ULN: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    303
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.48
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in Percentages
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.2
         upper limit
    		 2.8

    Primary: Percentage of Participants with Potassium Levels < Lower Limit of Normal (LLN)

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    End point title
    		 Percentage of Participants with Potassium Levels < Lower Limit of Normal (LLN)
    End point description
    Participants had potassium levels assessed throughout the 52-week treatment period. The percentage of participants who had any potassium level that was < the LLN of 3.5 mEq/L during the treatment phase is presented. The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    202
    101
    Units: Percentage of Participants
        number (not applicable)
    1.5
    1.0
    Statistical analysis title
    		 Potassium < LLN: Anacetrapib 100 mg vs.Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    303
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.722
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in Percentages
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 3.5

    Primary: Percentage of Participants with Bicarbonate Levels > ULN

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    End point title
    		 Percentage of Participants with Bicarbonate Levels > ULN
    End point description
    Participants had bicarbonate levels assessed throughout the 52-week treatment period. The percentage of participants who had any bicarbonate level that was > the ULN of 33 mEq/L during the treatment phase is presented. The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    202
    101
    Units: Percentage of Participants
        number (not applicable)
    0.0
    0.0
    Statistical analysis title
    		 Bicarbonate > ULN: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    303
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 > 0.999
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in Percentages
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.7
         upper limit
    		 1.9

    Primary: Percentage of Participants with Consecutive Changes in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) of >=3 x ULN

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    End point title
    		 Percentage of Participants with Consecutive Changes in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) of >=3 x ULN
    End point description
    Participants had AST and ALT levels assessed throughout the 52-week treatment period. The percentage of participants who had 2 consecutive assessments of either AST or ALT that were 3 x ULN or greater during the treatment phase is presented. The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    202
    101
    Units: Percentage of Participants
        number (not applicable)
    1.5
    1.0
    Statistical analysis title
    		 ALT/AST >=3 x ULN: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    303
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.722
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in Percentages
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 3.5

    Primary: Percentage of Participants with Creatine Kinase (CK) Level >=10 x ULN

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    End point title
    		 Percentage of Participants with Creatine Kinase (CK) Level >=10 x ULN
    End point description
    Participants had CK levels assessed throughout the 52-week treatment period. The percentage of participants who had any CK level that was >=10 x ULN during the treatment phase is presented. The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    202
    101
    Units: Percentage of Participants
        number (not applicable)
    0.0
    1.0
    Statistical analysis title
    		 CK >=10 x ULN: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    303
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.157
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in Percentages
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.4
         upper limit
    		 0.9

    Primary: Percentage of Participants with CK Level >=10 x ULN with Muscle Spasms

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    End point title
    		 Percentage of Participants with CK Level >=10 x ULN with Muscle Spasms
    End point description
    Participants had CK levels assessed throughout the 52-week treatment period. The percentage of participants who had any CK level that was >=10 x ULN and had associated muscle spasms during the treatment phase is presented. The analysis population consisted of all randomized participants who received at least one dose of study treatment and had at least one post-baseline test result that met pre-determined criteria.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    202
    101
    Units: Percentage of Participants
        number (not applicable)
    0.0
    1.0
    Statistical analysis title
    		 CK >=10 x ULN & Sp: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    303
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.157
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in Percentages
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.4
         upper limit
    		 0.9

    Primary: Percentage of Participants Adjudicated Cardiovascular (CV) SAE

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    End point title
    		 Percentage of Participants Adjudicated Cardiovascular (CV) SAE
    End point description
    An AE or suspected adverse reaction was considered an SAE if it resulted in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. All events were adjudicated by an expert committee independent of the Sponsor. The percentage of participants that experienced adjudicated SAEs of CV death, non-fatal stroke, non-fatal myocardial infarction, or unstable angina during the treatment phase is presented. The APaT population consisted of all randomized participants who received at least one dose of study treatment.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    203
    102
    Units: Percentage of Participants
        number (not applicable)
    1.5
    0.0
    Statistical analysis title
    		 CV SAE: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    305
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.218
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in Percentages
    Point estimate
    0.218
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.2
         upper limit
    		 4.3

    Primary: Percentage of Participants Who Died from Any Cause - Treatment Phase

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    End point title
    		 Percentage of Participants Who Died from Any Cause - Treatment Phase
    End point description
    The percentage of participants who died from any cause during the treatment phase is presented. All deaths were adjudicated by an expert committee independent of the Sponsor. The APaT population consisted of all randomized participants who received at least one dose of study treatment.
    End point type
    Primary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    203
    102
    Units: Percentage of Participants
        number (not applicable)
    0.0
    0.0
    Statistical analysis title
    		 Any Cause Death: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    305
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 > 0.999
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Difference in Percentages
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.6
         upper limit
    		 1.9

    Secondary: Percent Change from Baseline in High-Density Lipoprotein Cholesterol Levels

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    End point title
    		 Percent Change from Baseline in High-Density Lipoprotein Cholesterol Levels
    End point description
    The efficacy of adding anacetrapib 100 mg relative to placebo on plasma concentrations of high-density lipoprotein cholesterol (HDL-C) was evaluated at Week 0 (start of treatment phase) and Week 52 (end of treatment phase) or at discontinuation. The FAS population consisted of all randomized participants who received at least one dose of study treatment and had at least one post randomization observation for the analysis endpoint subsequent to at least one dose of study treatment, and had baseline data for those analyses that require baseline data.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 52
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    173
    88
    Units: Percent Change
        least squares mean (full range (min-max))
    105.8 (101.1 to 110.6)
    3.7 (-2.8 to 10.3)
    Statistical analysis title
    		 HDL: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in Least Squares (LS) Means
    Point estimate
    102.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 94.2
         upper limit
    		 110.1

    Secondary: Percent Change from Baseline in Non-High-Density Lipoprotein Cholesterol Levels

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    End point title
    		 Percent Change from Baseline in Non-High-Density Lipoprotein Cholesterol Levels
    End point description
    The efficacy of adding anacetrapib 100 mg was evaluated relative to placebo on plasma concentrations of non-high-density lipoprotein cholesterol (HDL-C) for the FAS population at Week 0 (start of treatment phase) and Week 52 (end of treatment phase) or at discontinuation. The FAS population consisted of all randomized participants who received at least one dose of study treatment and had at least one post randomization observation for the analysis endpoint subsequent to at least one dose of study treatment, and had baseline data for those analyses that require baseline data.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 52
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    173
    88
    Units: Percent Change
        least squares mean (full range (min-max))
    -32.0 (-35.1 to -28.9)
    4.4 (0.1 to 8.8)
    Statistical analysis title
    		 Non-HDL: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in LS Means
    Point estimate
    -36.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -41.7
         upper limit
    		 -31.1

    Secondary: Percent Change from Baseline in Apolipoprotein (Apo) B Levels

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    End point title
    		 Percent Change from Baseline in Apolipoprotein (Apo) B Levels
    End point description
    The efficacy of adding anacetrapib 100 mg was evaluated relative to placebo on plasma concentrations of apolipoprotein (Apo) B for the FAS population at Week 0 (start of treatment phase) and Week 52 (end of treatment phase) or at discontinuation. The FAS population consisted of all randomized participants who received at least one dose of study treatment and had at least one post randomization observation for the analysis endpoint subsequent to at least one dose of study treatment, and had baseline data for those analyses that require baseline data.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 52
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    173
    88
    Units: Percent Change
        number (confidence interval 95%)
    -19.6 (-22.5 to -16.8)
    5.2 (1.3 to 9.1)
    Statistical analysis title
    		 Apo B: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in LS Means
    Point estimate
    -24.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -29.5
         upper limit
    		 -20.1

    Secondary: Percent Change from Baseline in Apolipoprotein (Apo) A-1 Levels

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    End point title
    		 Percent Change from Baseline in Apolipoprotein (Apo) A-1 Levels
    End point description
    The efficacy of adding anacetrapib 100 mg was evaluated relative to placebo on plasma concentrations of Apo A-1 for the FAS population at Week 0 (start of treatment phase) and Week 52 (end of treatment phase) or at discontinuation. The FAS population consisted of all randomized participants who received at least one dose of study treatment and had at least one post randomization observation for the analysis endpoint subsequent to at least one dose of study treatment, and had baseline data for those analyses that require baseline data.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 52
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    173
    88
    Units: Percent Change
        number (confidence interval 95%)
    35.8 (33.0 to 38.6)
    2.9 (-1.0 to 6.8)
    Statistical analysis title
    		 Apo A-1: Anacetrapib 100 mg vs. Placebo
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Constrained Longitudinal Data Analysis
    Parameter type
    		 Difference in LS Means
    Point estimate
    32.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 28.2
         upper limit
    		 37.6

    Secondary: Percent Change from Baseline in Lipoprotein(a) (Lp[a]) Levels

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    End point title
    		 Percent Change from Baseline in Lipoprotein(a) (Lp[a]) Levels
    End point description
    The efficacy of adding anacetrapib 100 mg was evaluated relative to placebo on plasma concentrations of lipoprotein(a) (Lp[a]) for the FAS population at Week 0 (start of treatment phase) and Week 52 (end of treatment phase) or at discontinuation. The FAS population consisted of all randomized participants who received at least one dose of study treatment and had at least one post randomization observation for the analysis endpoint subsequent to at least one dose of study treatment, and had baseline data for those analyses that require baseline data.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 52
    End point values
    		 Anacetrapib 100 mg Placebo
    Number of subjects analysed
    174
    88
    Units: Percent Change
        number (confidence interval 95%)
    -31.8 (-37.4 to -26.3)
    0.0 (-5.1 to 5.1)
    Statistical analysis title
    		 Lp[a]: Anacetrapib 100 mg vs. Placebo
    Statistical analysis description
    Hodges-Lehmann estimate of the median difference between treatments with a corresponding distribution-free confidence interval (CI) based on Wilcoxon's rank sum test.
    Comparison groups
    Anacetrapib 100 mg v Placebo
    Number of subjects included in analysis
    262
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -27.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -34.7
         upper limit
    		 -21.2

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 64 weeks
    Adverse event reporting additional description
    Safety population: All participants who received at least 1 dose of study treatment. The treatment phase included AEs in 52-week period (first dose to last visit of treatment). The reversal phase included AEs in 12-week period after treatment phase (~Week 64).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Anacetrapib 100 mg - Treatment Phase
    Reporting group description
    		 Participants were administered one tablet of 100 mg anacetrapib orally once daily with a meal for 52 weeks.

    Reporting group title
    Placebo - Treatment Phase
    Reporting group description
    		 Participants were administered one matching placebo tablet orally once daily with a meal for 52 weeks.

    Reporting group title
    Anacetrapib 100 mg - Reversal Phase
    Reporting group description
    		 Safety data that was reported during the 12-week period from the day after the treatment phase to the participant’s last visit (discontinuation visit or week 64).

    Reporting group title
    Placebo - Reversal Phase
    Reporting group description
    		 Safety data that was reported during the 12-week period from the day after the treatment phase to the participant’s last visit (discontinuation visit or week 64).

    Serious adverse events
    		 Anacetrapib 100 mg - Treatment Phase Placebo - Treatment Phase Anacetrapib 100 mg - Reversal Phase Placebo - Reversal Phase
    Total subjects affected by serious adverse events
         subjects affected / exposed
    18 / 203 (8.87%)
    10 / 102 (9.80%)
    3 / 196 (1.53%)
    2 / 95 (2.11%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    1 / 203 (0.49%)
    1 / 102 (0.98%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 102 (0.98%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 102 (0.98%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Device malfunction
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug resistance
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Medical device discomfort
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Uterovaginal prolapse
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Emotional distress
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 102 (0.98%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Gastrointestinal anastomotic leak
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 102 (0.98%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 102 (0.00%)
    1 / 196 (0.51%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    4 / 203 (1.97%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 102 (0.98%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 102 (0.98%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 203 (0.49%)
    1 / 102 (0.98%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 102 (0.98%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 102 (0.00%)
    1 / 196 (0.51%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 102 (0.00%)
    1 / 196 (0.51%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Loss of consciousness
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 102 (0.98%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Migraine with aura
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 203 (0.00%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    1 / 95 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Pancreatitis
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal colic
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Endocarditis
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 102 (0.98%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 203 (0.49%)
    0 / 102 (0.00%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 203 (0.00%)
    1 / 102 (0.98%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Anacetrapib 100 mg - Treatment Phase Placebo - Treatment Phase Anacetrapib 100 mg - Reversal Phase Placebo - Reversal Phase
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    87 / 203 (42.86%)
    41 / 102 (40.20%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    16 / 203 (7.88%)
    6 / 102 (5.88%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences all number
    19
    7
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    16 / 203 (7.88%)
    9 / 102 (8.82%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences all number
    19
    10
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    12 / 203 (5.91%)
    2 / 102 (1.96%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences all number
    15
    2
    0
    0
    Myalgia
         subjects affected / exposed
    18 / 203 (8.87%)
    4 / 102 (3.92%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences all number
    26
    5
    0
    0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    2 / 203 (0.99%)
    6 / 102 (5.88%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences all number
    2
    7
    0
    0
    Influenza
         subjects affected / exposed
    20 / 203 (9.85%)
    11 / 102 (10.78%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences all number
    22
    11
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    40 / 203 (19.70%)
    19 / 102 (18.63%)
    0 / 196 (0.00%)
    0 / 95 (0.00%)
         occurrences all number
    50
    21
    0
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 Mar 2012
    AM 1: changed the LDL-C method for the primary efficacy endpoint from direct method to beta quantification method and for women of child- bearing potential to report pregnancy anytime during the 2 year time period after stopping study medication.
    01 Nov 2013
    AM 2: updated the contraception guidance to women of child- bearing potential and to implement pregnancy follow-up on an annual basis for up to 4 years after the last dose of study medication.
    19 Feb 2015
    AM3: Updated the annual pregnancy follow-up period for women of child-bearing potential (WOCBP) from 4 years to 5 years after the last dose of anacetrapib. Also contraception guidance for WOCBP was extended from 4 to 5 years after last dose of anacetrapib.

    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.
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
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