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MENDEL-2: Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2

Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT01763827
Collaborator
(none)
615
Enrollment
83
Locations
6
Arms
9.2
Actual Duration (Months)
7.4
Patients Per Site
0.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective was to evaluate the effect of 12 weeks of evolocumab subcutaneous (SC) monotherapy every 2 weeks (Q2W) and monthly (QM), compared with placebo and ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in adults with a 10-year Framingham risk score of 10% or less.

Condition or Disease Intervention/Treatment Phase
  • Biological: Evolocumab
  • Drug: Ezetimibe
  • Biological: Placebo to Evolocumab
  • Other: Placebo to Ezetimibe
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
615 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Double-blind, Randomized, Placebo and Ezetimibe-controlled, Multicenter Study to Evaluate Safety and Efficacy of Lipid Lowering Monotherapy With AMG 145 in Subjects With a 10-Year Framingham Risk Score of 10% or Less
Actual Study Start Date :
Jan 21, 2013
Actual Primary Completion Date :
Oct 10, 2013
Actual Study Completion Date :
Oct 29, 2013

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo Q2W

Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.

Biological: Placebo to Evolocumab
Administered by subcutaneous injection

Other: Placebo to Ezetimibe
Administered orally once daily
Placebo Comparator: Placebo QM

Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.

Biological: Placebo to Evolocumab
Administered by subcutaneous injection

Other: Placebo to Ezetimibe
Administered orally once daily
Active Comparator: Ezetimibe (Q2W)

Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.

Drug: Ezetimibe
Administered orally once a day
Other Names:
  • Zetia

    • Biological: Placebo to Evolocumab
    Administered by subcutaneous injection
    Active Comparator: Ezetimibe (QM)

    Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.

    Drug: Ezetimibe
    Administered orally once a day
    Other Names:
  • Zetia

    • Biological: Placebo to Evolocumab
    Administered by subcutaneous injection
    Experimental: Evolocumab Q2W

    Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.

    Biological: Evolocumab
    Administered by subcutaneous injection
    Other Names:
  • AMG 145
  • Repatha

    • Other: Placebo to Ezetimibe
    Administered orally once daily
    Experimental: Evolocumab QM

    Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.

    Biological: Evolocumab
    Administered by subcutaneous injection
    Other Names:
  • AMG 145
  • Repatha

    • Other: Placebo to Ezetimibe
    Administered orally once daily

    Outcome Measures

    Primary Outcome Measures

    1. Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12 [Baseline and Week 12]

    2. Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 [Baseline and Weeks 10 and 12]

    Secondary Outcome Measures

    1. Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 [Baseline and Weeks 10 and 12]

    2. Change From Baseline in LDL-C at Week 12 [Baseline and Week 12]

    3. Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL [Weeks 10 and 12]

    4. Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 [Week 12]

    5. Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12 [Baseline and Weeks 10 and 12]

    6. Percent Change From Baseline in Non-HDL-C at Week 12 [Baseline and Week 12]

    7. Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 [Baseline and Weeks 10 and 12]

    8. Percent Change From Baseline in Apolipoprotein B at Week 12 [Baseline and Week 12]

    9. Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at the Mean of Weeks 10 and 12 [Baseline and Weeks 10 and 12]

    10. Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at Week 12 [Baseline and Week 12]

    11. Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 [Baseline and Weeks 10 and 12]

    12. Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 [Baseline and Week 12]

    13. Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12 [Baseline and Weeks 10 and 12]

    14. Percent Change From Baseline in Lipoprotein (a) at Week 12 [Baseline and Week 12]

    15. Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 [Baseline and Weeks 10 and 12]

    16. Percent Change From Baseline in Triglycerides at Week 12 [Baseline and Week 12]

    17. Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12 [Baseline and Weeks 10 and 12]

    18. Percent Change From Baseline in VLDL-C at Week 12 [Baseline and Week 12]

    19. Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12 [Baseline and Weeks 10 and 12]

    20. Percent Change From Baseline in HDL-C at Week 12 [Baseline and Week 12]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Male or female ≥ 18 to ≤ 80 years of age

    • National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) Framingham risk score of 10% or less

    • Fasting LDL-C ≥ 100 mg/dL (2.6 mmol/L) and <190 mg/dL

    • Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

    Exclusion Criteria:

    • History of coronary heart disease

    • New York Heart Association (NYHA) III or IV heart failure

    • Uncontrolled cardiac arrhythmia

    • Uncontrolled hypertension

    • Diabetes mellitus (Type 1 diabetes, poorly controlled type 2 diabetes)

    • Uncontrolled hypothyroidism or hyperthyroidism

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Birmingham Alabama United States 35216
    2 Research Site Chandler Arizona United States 85224
    3 Research Site Little Rock Arkansas United States 72205
    4 Research Site Carmichael California United States 95608
    5 Research Site Encinitas California United States 92024
    6 Research Site San Diego California United States 92111
    7 Research Site Tustin California United States 92780
    8 Research Site Jacksonville Florida United States 32204
    9 Research Site Jacksonville Florida United States 32216
    10 Research Site Miami Florida United States 33144
    11 Research Site Ponte Vedra Florida United States 32081
    12 Research Site Sanford Florida United States 32771
    13 Research Site Boise Idaho United States 83704
    14 Research Site Chicago Illinois United States 60654
    15 Research Site Indianapolis Indiana United States 46260
    16 Research Site Overland Park Kansas United States 66202
    17 Research Site Louisville Kentucky United States 40213
    18 Research Site Bethesda Maryland United States 20817
    19 Research Site Brockton Massachusetts United States 02301
    20 Research Site Edina Minnesota United States 55435
    21 Research Site Olive Branch Mississippi United States 38654
    22 Research Site Las Vegas Nevada United States 89148
    23 Research Site Endwell New York United States 13760
    24 Research Site New Windsor New York United States 12553
    25 Research Site Raleigh North Carolina United States 27609
    26 Research Site Raleigh North Carolina United States 27612
    27 Research Site Fargo North Dakota United States 58103
    28 Research Site Akron Ohio United States 44311
    29 Research Site Cincinnati Ohio United States 45212
    30 Research Site Cincinnati Ohio United States 45236
    31 Research Site Cincinnati Ohio United States 45246
    32 Research Site Cleveland Ohio United States 44122
    33 Research Site Norman Oklahoma United States 73069
    34 Research Site Oklahoma City Oklahoma United States 73103
    35 Research Site Duncansville Pennsylvania United States 16635
    36 Research Site Anderson South Carolina United States 29621
    37 Research Site Mount Pleasant South Carolina United States 29464
    38 Research Site Rapid City South Dakota United States 57702
    39 Research Site Jackson Tennessee United States 38305
    40 Research Site Boerne Texas United States 78006
    41 Research Site Dallas Texas United States 75230
    42 Research Site San Antonio Texas United States 78205
    43 Research Site Salt Lake City Utah United States 84124
    44 Research Site Norfolk Virginia United States 23502
    45 Research Site Richmond Virginia United States 23294
    46 Research Site Renton Washington United States 98057
    47 Research Site Seattle Washington United States 98104
    48 Research Site Darlinghurst New South Wales Australia 2010
    49 Research Site Maroubra New South Wales Australia 2035
    50 Research Site Carina Heights Queensland Australia 4152
    51 Research Site Sherwood Queensland Australia 4075
    52 Research Site Anthée Belgium 5520
    53 Research Site Bruxelles Belgium 1080
    54 Research Site Gozee Belgium 6534
    55 Research Site Gribomont Belgium 6887
    56 Research Site Halen Belgium 3545
    57 Research Site Ham Belgium 3945
    58 Research Site Linkebeek Belgium 1630
    59 Research Site Retie Belgium 2470
    60 Research Site Tessenderlo Belgium 3980
    61 Research Site Bay Roberts Newfoundland and Labrador Canada A0A 1G0
    62 Research Site Mount Pearl Newfoundland and Labrador Canada A1N 1W7
    63 Research Site Toronto Ontario Canada M9W 4L6
    64 Research Site Granby Quebec Canada J2G 8Z9
    65 Research Site Aalborg Denmark 9000
    66 Research Site Ballerup Denmark 2750
    67 Research Site Vejle Denmark 7100
    68 Research Site Gières France 38610
    69 Research Site Grenoble Cedex 9 France 38043
    70 Research Site Seoul Korea, Republic of 120-752
    71 Research Site Seoul Korea, Republic of 135-710
    72 Research Site Seoul Korea, Republic of 138-736
    73 Research Site Alberton Gauteng South Africa 1449
    74 Research Site Johannesburg Gauteng South Africa 2196
    75 Research Site Parow Western Cape South Africa 7505
    76 Research Site Somerset West Western Cape South Africa 7130
    77 Research Site Worcester Western Cape South Africa 6850
    78 Research Site Bloemfontein South Africa 9301
    79 Research Site Kaohsiung Taiwan 807
    80 Research Site Kaohsiung Taiwan 83301
    81 Research Site Taipei Taiwan 100
    82 Research Site Istanbul Turkey 34093
    83 Research Site Istanbul Turkey 34662

    Sponsors and Collaborators

    • Amgen

    Investigators

    • Study Director: MD, Amgen

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT01763827
    Other Study ID Numbers:
    • 20110114
    First Posted:
    Jan 9, 2013
    Last Update Posted:
    Jul 20, 2020
    Last Verified:
    Jul 1, 2020
    Keywords provided by Amgen
    High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia
    Additional relevant MeSH terms:
    Hyperlipidemias
    Ezetimibe
    Evolocumab
    Antibodies, Monoclonal

    Study Results

    Participant Flow

    Recruitment Details Men and women ≥ 18 to ≤ 80 years of age with fasting low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL and < 190 mg/dL and fasting triglycerides ≤ 400 mg/dL with a 10-year Framingham Risk Score of 10% or less were eligible for this study. The first participant was enrolled on 21 January 2013 and the last participant was enrolled 29 July 2013.
    Pre-assignment Detail Participants received subcutaneous placebo corresponding to the once monthly dose volume during a 6 week screening period. Participants who completed the screening period and met final eligibility criteria were randomized 1:1:1:1:2:2 into 6 treatment groups. Randomization was stratified by LDL-C concentration (< 130 mg/dL or ≥ 30 mg/dL).
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Period Title: Overall Study
    STARTED 77 78 77 77 153 153
    Received at Least 1 Dose of Study Drug 76 78 77 77 153 153
    COMPLETED 74 77 73 76 147 151
    NOT COMPLETED 3 1 4 1 6 2

    Baseline Characteristics

    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM Total
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks. Total of all reporting groups
    Overall Participants 77 78 77 77 153 153 615
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    54.4
    (10.3)
    52.6
    (10.7)
    53.9
    (11.3)
    53.0
    (12.7)
    52.5
    (13.7)
    52.9
    (12.1)
    53.1
    (12.1)
    Sex: Female, Male (Count of Participants)
    Female
    49
    63.6%
    47
    60.3%
    53
    68.8%
    52
    67.5%
    104
    68%
    101
    66%
    406
    66%
    Male
    28
    36.4%
    31
    39.7%
    24
    31.2%
    25
    32.5%
    49
    32%
    52
    34%
    209
    34%
    Race/Ethnicity, Customized (participants) [Number]
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    1
    1.3%
    0
    0%
    2
    1.3%
    3
    0.5%
    Asian
    9
    11.7%
    8
    10.3%
    7
    9.1%
    10
    13%
    12
    7.8%
    12
    7.8%
    58
    9.4%
    Black or African American
    4
    5.2%
    6
    7.7%
    6
    7.8%
    6
    7.8%
    9
    5.9%
    9
    5.9%
    40
    6.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    1
    1.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.2%
    White
    64
    83.1%
    63
    80.8%
    63
    81.8%
    60
    77.9%
    132
    86.3%
    129
    84.3%
    511
    83.1%
    Other
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Mixed Race
    0
    0%
    0
    0%
    1
    1.3%
    0
    0%
    0
    0%
    1
    0.7%
    2
    0.3%
    Race/Ethnicity, Customized (participants) [Number]
    Hispanic or Latino
    6
    7.8%
    8
    10.3%
    9
    11.7%
    11
    14.3%
    14
    9.2%
    21
    13.7%
    69
    11.2%
    Not Hispanic or Latino
    71
    92.2%
    70
    89.7%
    68
    88.3%
    66
    85.7%
    139
    90.8%
    132
    86.3%
    546
    88.8%
    Stratification Factor: Low-density Lipoprotein Cholesterol (LDL-C) (participants) [Number]
    < 130 mg/dL
    23
    29.9%
    24
    30.8%
    22
    28.6%
    22
    28.6%
    45
    29.4%
    45
    29.4%
    181
    29.4%
    ≥ 130 mg/dL
    54
    70.1%
    54
    69.2%
    55
    71.4%
    55
    71.4%
    108
    70.6%
    108
    70.6%
    434
    70.6%
    LDL-C Concentration (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    139.5
    (21.3)
    144.3
    (23.9)
    143.3
    (23.8)
    143.5
    (23.1)
    141.7
    (22.3)
    144.4
    (23.3)
    142.9
    (22.9)
    Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) Concentration (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    167.4
    (25.8)
    172.8
    (31.0)
    168.8
    (28.9)
    169.4
    (27.3)
    166.5
    (25.6)
    170.4
    (26.6)
    169.0
    (27.2)
    Apolipoprotein B Concentration (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    103.7
    (16.8)
    107.3
    (19.9)
    107.2
    (19.7)
    106.2
    (17.8)
    104.5
    (17.2)
    108.3
    (17.9)
    106.2
    (18.1)
    Total Cholesterol/High-density Lipoprotein Cholesterol Ratio (ratio) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [ratio]
    4.148
    (1.311)
    4.444
    (1.465)
    4.055
    (1.082)
    4.335
    (1.118)
    4.170
    (1.170)
    4.175
    (1.071)
    4.210
    (1.191)
    Apolipoprotein B/Apolipoprotein A-1 Ratio (ratio) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [ratio]
    0.671
    (0.193)
    0.713
    (0.194)
    0.691
    (0.187)
    0.712
    (0.173)
    0.687
    (0.169)
    0.707
    (0.170)
    0.697
    (0.178)
    Lipoprotein(a) (nmol/L) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [nmol/L]
    21.0
    (62.9)
    21.5
    (84.0)
    28.0
    (79.1)
    28.0
    (65.7)
    20.0
    (61.5)
    28.0
    (86.9)
    25.0
    (74.5)
    Triglycerides (mg/dL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [mg/dL]
    113.5
    (74.7)
    118.0
    (83.4)
    112.5
    (64.9)
    116.5
    (52.4)
    112.0
    (62.6)
    119.0
    (59.1)
    115.3
    (65.5)
    Very Low-density Lipoprotein Cholesterol (VLDL-C) Concentration (mg/dL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [mg/dL]
    22.5
    (13.2)
    23.8
    (15.4)
    22.5
    (12.4)
    23.5
    (10.5)
    22.5
    (11.5)
    23.5
    (11.8)
    23.0
    (12.4)
    High-density Lipoprotein Cholesterol (HDL-C) Concentration (mg/dL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [mg/dL]
    57.0
    (23.6)
    54.0
    (17.8)
    58.5
    (16.8)
    53.5
    (18.5)
    53.0
    (18.0)
    56.5
    (18.0)
    55.3
    (18.7)

    Outcome Measures

    1. Primary Outcome
    Title Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12
    Description
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Least Squares Mean (Standard Error) [percent change]
    0.10
    (1.67)
    -1.34
    (1.54)
    -17.75
    (1.67)
    -18.57
    (1.56)
    -57.04
    (1.23)
    -56.12
    (1.12)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model included treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -57.14
    Confidence Interval (2-Sided) 95%
    -61.14 to -53.14
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.03
    Estimation Comments Placebo is the reference
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -54.78
    Confidence Interval (2-Sided) 95%
    -58.46 to -51.10
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.87
    Estimation Comments Placebo is the reference
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and ezetimibe, and the alternative hypothesis was that a mean difference did exist.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -39.29
    Confidence Interval (2-Sided) 95%
    -43.28 to -35.31
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.03
    Estimation Comments Ezetimibe is the reference
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and ezetimibe, and the alternative hypothesis was that a mean difference did exist.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -37.55
    Confidence Interval (2-Sided) 95%
    -41.24 to -33.86
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.88
    Estimation Comments Ezetimibe is the reference
    2. Primary Outcome
    Title Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
    Description
    Time Frame Baseline and Weeks 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Least Squares Mean (Standard Error) [percent change]
    -0.43
    (1.45)
    -1.41
    (1.37)
    -17.52
    (1.46)
    -19.12
    (1.39)
    -56.93
    (1.07)
    -58.81
    (1.00)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments The null hypothesis was that there was no mean difference in the percent change from Baseline at the mean of Weeks 10 and 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -56.50
    Confidence Interval (2-Sided) 95%
    -59.95 to -53.04
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.76
    Estimation Comments Placebo is the reference
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments The null hypothesis was that there was no mean difference in the percent change from Baseline at the mean of Weeks 10 and 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -57.40
    Confidence Interval (2-Sided) 95%
    -60.66 to -54.14
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.66
    Estimation Comments Placebo is the reference
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments The null hypothesis was that there was no mean difference in the percent change from Baseline at the mean of Weeks 10 and 12 in LDL-C between evolocumab and ezetimibe, and the alternative hypothesis was that a mean difference did exist.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -39.41
    Confidence Interval (2-Sided) 95%
    -42.87 to -35.94
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.76
    Estimation Comments Ezetimibe is the reference
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments The null hypothesis was that there was no mean difference in the percent change from Baseline at the mean of Weeks 10 and 12 in LDL-C between evolocumab and ezetimibe, and the alternative hypothesis was that a mean difference did exist.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -36.69
    Confidence Interval (2-Sided) 95%
    -42.97 to -36.42
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.66
    Estimation Comments Ezetimibe is the reference
    3. Secondary Outcome
    Title Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
    Description
    Time Frame Baseline and Weeks 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Least Squares Mean (Standard Error) [mg/dL]
    1.2
    (2.3)
    0.0
    (2.1)
    -23.1
    (2.3)
    -25.9
    (2.1)
    -78.4
    (1.7)
    -81.9
    (1.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -79.6
    Confidence Interval (2-Sided) 95%
    -85.0 to -74.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.7
    Estimation Comments Placebo is the reference
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -81.9
    Confidence Interval (2-Sided) 95%
    -87.0 to -76.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.6
    Estimation Comments Placebo is the reference
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -55.3
    Confidence Interval (2-Sided) 95%
    -60.7 to -49.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.7
    Estimation Comments Ezetimibe is the reference
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -56.1
    Confidence Interval (2-Sided) 95%
    -61.1 to -51.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.6
    Estimation Comments Ezetimibe is the reference
    4. Secondary Outcome
    Title Change From Baseline in LDL-C at Week 12
    Description
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Least Squares Mean (Standard Error) [mg/dL]
    1.9
    (2.5)
    -0.1
    (2.4)
    -23.4
    (2.5)
    -25.0
    (2.4)
    -78.4
    (1.9)
    -77.9
    (1.7)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -80.4
    Confidence Interval (2-Sided) 95%
    -86.4 to -74.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.1
    Estimation Comments Placebo is the reference
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -77.8
    Confidence Interval (2-Sided) 95%
    -83.4 to -72.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.8
    Estimation Comments Placebo is the reference
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -55.0
    Confidence Interval (2-Sided) 95%
    -61.1 to -49.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.1
    Estimation Comments Ezetimibe was the reference
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, stratification factor, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -52.9
    Confidence Interval (2-Sided) 95%
    -58.5 to -47.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.9
    Estimation Comments Ezetimibe was the reference
    5. Secondary Outcome
    Title Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL
    Description
    Time Frame Weeks 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Number (95% Confidence Interval) [percentage of participants]
    0.0
    0%
    0.0
    0%
    1.3
    1.7%
    2.8
    3.6%
    73.6
    48.1%
    71.3
    46.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Cochran-Mantel-Haenszel
    Comments Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 73.6
    Confidence Interval (2-Sided) 95%
    64.4 to 80.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Cochran-Mantel-Haenszel
    Comments Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 71.3
    Confidence Interval (2-Sided) 95%
    62.2 to 78.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Cochran-Mantel-Haenszel
    Comments Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 72.2
    Confidence Interval (2-Sided) 95%
    62.4 to 78.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Cochran-Mantel-Haenszel
    Comments Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 68.6
    Confidence Interval (2-Sided) 95%
    58.3 to 75.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12
    Description
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Number (95% Confidence Interval) [percentage of participants]
    1.4
    1.8%
    0.0
    0%
    1.4
    1.8%
    1.4
    1.8%
    72.9
    47.6%
    65.4
    42.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Cochran-Mantel-Haenszel
    Comments Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 71.5
    Confidence Interval (2-Sided) 95%
    61.2 to 78.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Cochran-Mantel-Haenszel
    Comments Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 65.4
    Confidence Interval (2-Sided) 95%
    55.6 to 72.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Cochran-Mantel-Haenszel
    Comments Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 71.5
    Confidence Interval (2-Sided) 95%
    61.3 to 78.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Cochran-Mantel-Haenszel
    Comments Based on CMH test stratified by Baseline LDL-C level. For testing, non-achievement was imputed for participants with a missing value.
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 64.0
    Confidence Interval (2-Sided) 95%
    53.5 to 71.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12
    Description
    Time Frame Baseline and Weeks 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Least Squares Mean (Standard Error) [percent change]
    -1.41
    (1.34)
    1.32
    (1.24)
    -14.64
    (1.35)
    -16.48
    (1.25)
    -50.22
    (0.99)
    -51.96
    (0.90)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -48.81
    Confidence Interval (2-Sided) 95%
    -52.01 to -45.61
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.63
    Estimation Comments Placebo is the reference
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -53.28
    Confidence Interval (2-Sided) 95%
    -56.23 to -50.33
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.50
    Estimation Comments Placebo is the reference
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -35.58
    Confidence Interval (2-Sided) 95%
    -38.79 to -32.38
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.63
    Estimation Comments Ezetimibe is the reference
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -35.49
    Confidence Interval (2-Sided) 95%
    -38.44 to -32.53
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.50
    Estimation Comments Ezetimibe is the reference
    8. Secondary Outcome
    Title Percent Change From Baseline in Non-HDL-C at Week 12
    Description
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Least Squares Mean (Standard Error) [percent change]
    -0.31
    (1.48)
    1.51
    (1.38)
    -14.89
    (1.47)
    -16.48
    (1.39)
    -50.12
    (1.08)
    -49.68
    (1.01)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -49.81
    Confidence Interval (2-Sided) 95%
    -53.34 to -46.27
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.79
    Estimation Comments Placebo is the reference
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -51.19
    Confidence Interval (2-Sided) 95%
    -54.49 to -47.90
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.67
    Estimation Comments Placebo is the reference
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -35.23
    Confidence Interval (2-Sided) 95%
    -38.74 to -31.71
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.78
    Estimation Comments Ezetimibe is the reference
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -33.21
    Confidence Interval (2-Sided) 95%
    -36.51 to -29.90
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.68
    Estimation Comments Ezetimibe is the reference
    9. Secondary Outcome
    Title Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
    Description
    Time Frame Baseline and Weeks 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Least Squares Mean (Standard Error) [percent change]
    0.05
    (1.51)
    1.54
    (1.41)
    -13.47
    (1.52)
    -14.75
    (1.43)
    -47.04
    (1.12)
    -49.39
    (1.03)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -47.09
    Confidence Interval (2-Sided) 95%
    -50.67 to -43.51
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.82
    Estimation Comments Placebo is the reference
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -50.93
    Confidence Interval (2-Sided) 95%
    -54.27 to -47.59
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.70
    Estimation Comments Placebo is the reference
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -33.57
    Confidence Interval (2-Sided) 95%
    -37.15 to -29.99
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.82
    Estimation Comments Ezetimibe is the reference
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -34.64
    Confidence Interval (2-Sided) 95%
    -37.99 to -31.28
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.71
    Estimation Comments Ezetimibe is the reference
    10. Secondary Outcome
    Title Percent Change From Baseline in Apolipoprotein B at Week 12
    Description
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Least Squares Mean (Standard Error) [percent change]
    0.59
    (1.58)
    1.84
    (1.53)
    -13.17
    (1.58)
    -14.02
    (1.54)
    -47.21
    (1.17)
    -46.59
    (1.12)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -47.81
    Confidence Interval (2-Sided) 95%
    -51.56 to -44.05
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.91
    Estimation Comments Placebo is the reference
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -48.43
    Confidence Interval (2-Sided) 95%
    -52.07 to -44.79
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.85
    Estimation Comments Placebo is the reference
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -34.04
    Confidence Interval (2-Sided) 95%
    -37.78 to -30.30
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.90
    Estimation Comments Ezetimibe is the reference
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -32.57
    Confidence Interval (2-Sided) 95%
    -36.21 to -28.92
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.85
    Estimation Comments Ezetimibe is the reference
    11. Secondary Outcome
    Title Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at the Mean of Weeks 10 and 12
    Description
    Time Frame Baseline and Weeks 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Least Squares Mean (Standard Error) [percent change]
    0.44
    (1.29)
    6.42
    (1.50)
    -9.14
    (1.29)
    -11.90
    (1.51)
    -38.49
    (0.95)
    -39.41
    (1.08)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -38.93
    Confidence Interval (2-Sided) 95%
    -42.00 to -35.86
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.56
    Estimation Comments Placebo is the reference
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -45.83
    Confidence Interval (2-Sided) 95%
    -49.39 to -42.27
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.81
    Estimation Comments Placebo is the reference
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -29.36
    Confidence Interval (2-Sided) 95%
    -32.43 to -26.28
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.56
    Estimation Comments Ezetimibe is the reference
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -27.51
    Confidence Interval (2-Sided) 95%
    -31.08 to -23.94
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.81
    Estimation Comments Ezetimibe is the reference
    12. Secondary Outcome
    Title Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at Week 12
    Description
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Least Squares Mean (Standard Error) [percent change]
    1.18
    (1.39)
    7.02
    (1.67)
    -10.03
    (1.39)
    -12.34
    (1.68)
    -38.45
    (1.02)
    -37.65
    (1.21)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -39.63
    Confidence Interval (2-Sided) 95%
    -42.97 to -36.30
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.69
    Estimation Comments Placebo is the reference
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -44.67
    Confidence Interval (2-Sided) 95%
    -48.66 to -40.68
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.03
    Estimation Comments Placebo is the reference
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -28.42
    Confidence Interval (2-Sided) 95%
    -31.73 to -25.10
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.68
    Estimation Comments Ezetimibe is the reference
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -25.31
    Confidence Interval (2-Sided) 95%
    -29.31 to -21.31
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.03
    Estimation Comments Ezetimibe is the reference
    13. Secondary Outcome
    Title Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12
    Description
    Time Frame Baseline and Weeks 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Least Squares Mean (Standard Error) [percent change]
    1.01
    (1.69)
    3.85
    (1.77)
    -13.39
    (1.69)
    -14.49
    (1.79)
    -48.12
    (1.25)
    -51.10
    (1.29)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -49.12
    Confidence Interval (2-Sided) 95%
    -53.12 to -45.12
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.03
    Estimation Comments Placebo is the reference
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -54.95
    Confidence Interval (2-Sided) 95%
    -59.12 to -50.78
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.12
    Estimation Comments Placebo is the reference
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -34.73
    Confidence Interval (2-Sided) 95%
    -38.73 to -30.73
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.03
    Estimation Comments Ezetimibe is the reference
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -36.62
    Confidence Interval (2-Sided) 95%
    -40.81 to -32.42
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.13
    Estimation Comments Ezetimibe is the reference
    14. Secondary Outcome
    Title Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
    Description
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Least Squares Mean (Standard Error) [percent change]
    1.12
    (1.77)
    4.51
    (1.90)
    -12.69
    (1.77)
    -14.29
    (1.92)
    -48.45
    (1.31)
    -48.26
    (1.39)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -49.57
    Confidence Interval (2-Sided) 95%
    -53.78 to -45.36
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.14
    Estimation Comments Placebo is the reference
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -52.77
    Confidence Interval (2-Sided) 95%
    -57.28 to -48.26
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.29
    Estimation Comments Placebo is the reference
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -35.76
    Confidence Interval (2-Sided) 95%
    -39.95 to -31.57
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.13
    Estimation Comments Ezetimibe is the reference
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Repeated measures linear effects model
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -33.97
    Confidence Interval (2-Sided) 95%
    -38.48 to -29.45
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.29
    Estimation Comments Ezetimibe is the reference
    15. Secondary Outcome
    Title Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12
    Description
    Time Frame Baseline and Weeks 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Median (Inter-Quartile Range) [percent change]
    0.12
    (2.72)
    0.00
    (2.96)
    0.00
    (2.72)
    -2.08
    (3.01)
    -18.37
    (2.02)
    -19.24
    (2.17)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -18.48
    Confidence Interval (2-Sided) 95%
    -25.28 to -11.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -19.24
    Confidence Interval (2-Sided) 95%
    -23.20 to -15.28
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -18.37
    Confidence Interval (2-Sided) 95%
    -24.39 to -12.35
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -17.15
    Confidence Interval (2-Sided) 95%
    -23.23 to -11.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    16. Secondary Outcome
    Title Percent Change From Baseline in Lipoprotein (a) at Week 12
    Description
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Median (Inter-Quartile Range) [percent change]
    0.00
    (2.75)
    0.00
    (3.26)
    0.00
    (2.75)
    -2.05
    (3.28)
    -20.41
    (2.04)
    -17.82
    (2.39)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -20.41
    Confidence Interval (2-Sided) 95%
    -27.76 to -13.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -17.82
    Confidence Interval (2-Sided) 95%
    -24.51 to -11.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -20.41
    Confidence Interval (2-Sided) 95%
    -28.13 to -12.69
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -15.77
    Confidence Interval (2-Sided) 95%
    -24.39 to -7.14
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    17. Secondary Outcome
    Title Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
    Description
    Time Frame Baseline and Weeks 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Median (Inter-Quartile Range) [percent change]
    -3.89
    (3.64)
    4.89
    (4.02)
    -1.46
    (3.60)
    -3.97
    (4.04)
    -9.16
    (2.65)
    -15.71
    (2.92)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.72
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -5.27
    Confidence Interval (2-Sided) 95%
    -13.27 to 2.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -20.59
    Confidence Interval (2-Sided) 95%
    -30.98 to -10.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.027
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -7.71
    Confidence Interval (2-Sided) 95%
    -16.86 to 1.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.044
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -11.73
    Confidence Interval (2-Sided) 95%
    -21.19 to -2.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    18. Secondary Outcome
    Title Percent Change From Baseline in Triglycerides at Week 12
    Description
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Median (Inter-Quartile Range) [percent change]
    -1.91
    (3.13)
    2.01
    (3.86)
    0.00
    (3.15)
    -2.41
    (3.89)
    -8.14
    (2.31)
    -15.64
    (2.78)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.72
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -6.23
    Confidence Interval (2-Sided) 95%
    -16.41 to 3.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -17.65
    Confidence Interval (2-Sided) 95%
    -26.67 to -8.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.027
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -8.14
    Confidence Interval (2-Sided) 95%
    -17.54 to 1.26
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.044
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -13.23
    Confidence Interval (2-Sided) 95%
    -21.69 to -4.77
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    19. Secondary Outcome
    Title Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12
    Description
    Time Frame Baseline and Weeks 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Median (Inter-Quartile Range) [percent change]
    -3.81
    (3.09)
    4.22
    (3.70)
    -2.69
    (3.12)
    -3.33
    (3.69)
    -8.40
    (2.28)
    -16.17
    (2.65)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.072
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -4.59
    Confidence Interval (2-Sided) 95%
    -11.30 to 2.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -20.39
    Confidence Interval (2-Sided) 95%
    -30.11 to -10.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.082
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -5.71
    Confidence Interval (2-Sided) 95%
    -14.13 to 2.71
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.044
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baselie value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -12.84
    Confidence Interval (2-Sided) 95%
    -22.14 to -3.54
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    20. Secondary Outcome
    Title Percent Change From Baseline in VLDL-C at Week 12
    Description
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Ful analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Median (Inter-Quartile Range) [percent change]
    -1.58
    (3.67)
    0.00
    (3.93)
    -0.94
    (3.65)
    -3.61
    (3.87)
    -9.52
    (2.64)
    -16.33
    (2.80)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.72
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -7.94
    Confidence Interval (2-Sided) 95%
    -18.81 to 2.92
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -16.33
    Confidence Interval (2-Sided) 95%
    -25.64 to -7.02
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.082
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -8.58
    Confidence Interval (2-Sided) 95%
    -18.10 to 0.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.044
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments The model includes treatment group, Baseline LDL-C level, scheduled visit and the interaction of treatment with scheduled visit as covariates.
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value -12.72
    Confidence Interval (2-Sided) 95%
    -20.89 to -4.54
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    21. Secondary Outcome
    Title Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12
    Description
    Time Frame Baseline and Weeks 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Median (Inter-Quartile Range) [percent change]
    -1.64
    (1.26)
    -4.67
    (1.32)
    -0.92
    (1.27)
    0.00
    (1.33)
    3.89
    (0.93)
    3.81
    (0.95)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.007
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value 5.53
    Confidence Interval (2-Sided) 95%
    2.23 to 8.84
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value 8.48
    Confidence Interval (2-Sided) 95%
    5.53 to 11.43
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.013
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value 4.81
    Confidence Interval (2-Sided) 95%
    0.85 to 8.78
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.044
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline visit
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value 3.81
    Confidence Interval (2-Sided) 95%
    -0.77 to 8.39
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    22. Secondary Outcome
    Title Percent Change From Baseline in HDL-C at Week 12
    Description
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    Measure Participants 76 78 77 77 153 153
    Median (Inter-Quartile Range) [percent change]
    -1.15
    (1.43)
    -5.27
    (1.40)
    -2.79
    (1.42)
    -1.47
    (1.41)
    4.76
    (1.05)
    4.06
    (1.01)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.007
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value 5.91
    Confidence Interval (2-Sided) 95%
    1.67 to 10.16
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value 9.33
    Confidence Interval (2-Sided) 95%
    5.32 to 13.34
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (Q2W), Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.013
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value 7.56
    Confidence Interval (2-Sided) 95%
    3.11 to 12.00
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Ezetimibe (QM), Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.044
    Comments Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
    Method Quade test
    Comments Adjusted for Baseline value
    Method of Estimation Estimation Parameter Median Treatment Difference
    Estimated Value 5.53
    Confidence Interval (2-Sided) 95%
    2.22 to 8.84
    Parameter Dispersion Type:
    Value:
    Estimation Comments Median difference and 95% CI were obtained from McKean-Schrader algorithm.

    Adverse Events

    Time Frame From the first dose of blinded investigational product until the end of the study (up to 14 weeks).
    Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
    Arm/Group Title Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks. Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
    All Cause Mortality
    Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/76 (0%) 1/78 (1.3%) 0/77 (0%) 1/77 (1.3%) 3/153 (2%) 1/153 (0.7%)
    Gastrointestinal disorders
    Pancreatitis acute 0/76 (0%) 0/78 (0%) 0/77 (0%) 0/77 (0%) 0/153 (0%) 1/153 (0.7%)
    Injury, poisoning and procedural complications
    Upper limb fracture 0/76 (0%) 0/78 (0%) 0/77 (0%) 0/77 (0%) 1/153 (0.7%) 0/153 (0%)
    Investigations
    Hepatic enzyme increased 0/76 (0%) 0/78 (0%) 0/77 (0%) 0/77 (0%) 1/153 (0.7%) 0/153 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder cancer 0/76 (0%) 1/78 (1.3%) 0/77 (0%) 0/77 (0%) 0/153 (0%) 0/153 (0%)
    Breast cancer 0/76 (0%) 0/78 (0%) 0/77 (0%) 1/77 (1.3%) 0/153 (0%) 0/153 (0%)
    Renal cancer 0/76 (0%) 0/78 (0%) 0/77 (0%) 0/77 (0%) 1/153 (0.7%) 0/153 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 0/76 (0%) 0/78 (0%) 0/77 (0%) 0/77 (0%) 1/153 (0.7%) 0/153 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo Q2W Placebo QM Ezetimibe (Q2W) Ezetimibe (QM) Evolocumab Q2W Evolocumab QM
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/76 (11.8%) 4/78 (5.1%) 10/77 (13%) 4/77 (5.2%) 12/153 (7.8%) 12/153 (7.8%)
    Gastrointestinal disorders
    Diarrhoea 5/76 (6.6%) 1/78 (1.3%) 2/77 (2.6%) 1/77 (1.3%) 4/153 (2.6%) 5/153 (3.3%)
    Infections and infestations
    Nasopharyngitis 1/76 (1.3%) 2/78 (2.6%) 4/77 (5.2%) 2/77 (2.6%) 3/153 (2%) 3/153 (2%)
    Nervous system disorders
    Headache 3/76 (3.9%) 1/78 (1.3%) 4/77 (5.2%) 1/77 (1.3%) 5/153 (3.3%) 5/153 (3.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.

    Results Point of Contact

    Name/Title Study Director
    Organization Amgen Inc.
    Phone 866-572-6436
    Email
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT01763827
    Other Study ID Numbers:
    • 20110114
    First Posted:
    Jan 9, 2013
    Last Update Posted:
    Jul 20, 2020
    Last Verified:
    Jul 1, 2020