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RUTHERFORD-2: Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study-2

Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT01763918
Collaborator
(none)
331
Enrollment
39
Locations
4
Arms
10.3
Actual Duration (Months)
8.5
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 subcutaneously once every 2 weeks (Q2W) and once monthly (QM), compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in adults with heterozygous familial hypercholesterolemia (HeFH).

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

Study Design

Study Type:
Interventional
Actual Enrollment :
331 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-controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 on LDL-C in Subjects With Heterozygous Familial Hypercholesterolemia
Actual Study Start Date :
Feb 7, 2013
Actual Primary Completion Date :
Nov 27, 2013
Actual Study Completion Date :
Dec 19, 2013

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo Q2W

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

Drug: Placebo
Administered by subcutaneous injection
Placebo Comparator: Placebo QM

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

Drug: Placebo
Administered by subcutaneous injection
Experimental: Evolocumab Q2W

Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks.

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

    		•
    Experimental: Evolocumab QM

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

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percent Change From Baseline in 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 With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L) [Weeks 10 and 12]

    4. Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) 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 the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 [Baseline and Weeks 10 and 12]

    10. Percent Change From Baseline in the Total Cholesterol/HDL-C 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 HDL-C at the Mean of Weeks 10 and 12 [Baseline and Weeks 10 and 12]

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

    19. 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]

    20. Percent Change From Baseline in VLDL-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

    • Diagnosis of heterozygous familial hypercholesterolemia

    • On a stable dose of an approved statin and lipid regulating medication

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

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

    Exclusion Criteria:

    • Homozygous familial hypercholesterolemia

    • LDL or plasma apheresis

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

    • Uncontrolled cardiac arrhythmia

    • Uncontrolled hypertension

    • 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 Scottsdale Arizona United States 85258
    2 Research Site Cincinnati Ohio United States 45227
    3 Research Site Camperdown New South Wales Australia 2015
    4 Research Site Perth Western Australia Australia 6000
    5 Research Site Vancouver British Columbia Canada V6Z 1Y6
    6 Research Site London Ontario Canada N6A 5K8
    7 Research Site Chicoutimi Quebec Canada G7H 7K9
    8 Research Site Montreal Quebec Canada H2W 1R7
    9 Research Site Montreal Quebec Canada H3A 1A1
    10 Research Site Bron France 69677
    11 Research Site Nantes Cedex 1 France 44093
    12 Research Site Paris Cedex 13 France 75651
    13 Research Site Köln Germany 50937
    14 Research Site New Territories Hong Kong
    15 Research Site Amersfoort Netherlands 3813 TZ
    16 Research Site Amsterdam Netherlands 1091 AC
    17 Research Site Amsterdam Netherlands 1105 AZ
    18 Research Site Gouda Netherlands 2803 HH
    19 Research Site Groningen Netherlands 9713 GZ
    20 Research Site Hoorn Netherlands 1625 HV
    21 Research Site Tilburg Netherlands 5022 GC
    22 Research Site Utrecht Netherlands 3584 CX
    23 Research Site Christchurch New Zealand 8011
    24 Research Site Oslo Norway 0373
    25 Research Site Johannesburg Gauteng South Africa 2193
    26 Research Site Midrand Gauteng South Africa 1685
    27 Research Site Observatory Western Cape South Africa 7925
    28 Research Site Parow Western Cape South Africa 7505
    29 Research Site Cordoba Andalucía Spain 14004
    30 Research Site Zaragoza Aragón Spain 50009
    31 Research Site Reus Cataluña Spain 43204
    32 Research Site Madrid Spain 28040
    33 Research Site Stockholm Sweden 111 35
    34 Research Site Stockholm Sweden 141 86
    35 Research Site Reinach Switzerland 4153
    36 Research Site Coventry United Kingdom CV2 2DX
    37 Research Site London United Kingdom SE1 7EH
    38 Research Site London United Kingdom W6 8RF
    39 Research Site Manchester United Kingdom M13 9WL

    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:
    NCT01763918
    Other Study ID Numbers:
    • 20110117
    • 2012-001365-32
    First Posted:
    Jan 9, 2013
    Last Update Posted:
    Jun 17, 2019
    Last Verified:
    Jun 1, 2019
    Keywords provided by Amgen
    High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia
    Additional relevant MeSH terms:
    Hyperlipoproteinemia Type II
    Hypercholesterolemia
    Hyperlipidemias
    Evolocumab

    Study Results

    Participant Flow

    Recruitment Details Men and women 18 to 80 years old with a diagnosis of heterozygous familial hypercholesterolemia (HeFH) on stable doses of an approved statin with fasting low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL were eligible for this study. The first participant enrolled on 07 February 2013 and the last participant enrolled 03 September 2013.
    Pre-assignment Detail Participants received subcutaneous placebo corresponding to the once monthly dose volume during a 6-week screening period. Those who completed the screening period and met final eligibility criteria were randomized 1:1:2:2 into 4 treatment groups. Randomization was stratified by LDL-C level (< 160 mg/dL vs ≥ 160 mg/dL) and ezetimibe use.
    Arm/Group Title Placebo Q2W Placebo QM Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Period Title: Overall Study
    STARTED 55 55 111 110
    Received Treatment 54 55 110 110
    COMPLETED 49 54 101 108
    NOT COMPLETED 6 1 10 2

    Baseline Characteristics

    Arm/Group Title Placebo Q2W Placebo QM Evolocumab Q2W Evolocumab QM Total
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Total of all reporting groups
    Overall Participants 55 55 111 110 331
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    51.1
    (14.1)
    46.8
    (12.1)
    52.3
    (12.6)
    51.9
    (12.0)
    51.1
    (12.7)
    Sex: Female, Male (Count of Participants)
    Female
    25
    45.5%
    24
    43.6%
    45
    40.5%
    46
    41.8%
    140
    42.3%
    Male
    30
    54.5%
    31
    56.4%
    66
    59.5%
    64
    58.2%
    191
    57.7%
    Race/Ethnicity, Customized (participants) [Number]
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    1.8%
    3
    5.5%
    4
    3.6%
    8
    7.3%
    16
    4.8%
    Black or African American
    1
    1.8%
    0
    0%
    1
    0.9%
    1
    0.9%
    3
    0.9%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    51
    92.7%
    49
    89.1%
    100
    90.1%
    98
    89.1%
    298
    90%
    Other
    2
    3.6%
    3
    5.5%
    6
    5.4%
    3
    2.7%
    14
    4.2%
    Race/Ethnicity, Customized (participants) [Number]
    Hispanic or Latino
    1
    1.8%
    0
    0%
    0
    0%
    1
    0.9%
    2
    0.6%
    Not Hispanic or Latino
    54
    98.2%
    55
    100%
    111
    100%
    109
    99.1%
    329
    99.4%
    Stratification Factor: Low-Density Lipoprotein Cholesterol (LDL-C) Level (participants) [Number]
    < 160 mg/dL
    35
    63.6%
    35
    63.6%
    70
    63.1%
    70
    63.6%
    210
    63.4%
    ≥ 160 mg/dL
    20
    36.4%
    20
    36.4%
    41
    36.9%
    40
    36.4%
    121
    36.6%
    Baseline Ezetimibe Use (participants) [Number]
    No
    22
    40%
    21
    38.2%
    43
    38.7%
    43
    39.1%
    129
    39%
    Yes
    33
    60%
    34
    61.8%
    68
    61.3%
    67
    60.9%
    202
    61%
    LDL-C Concentration (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    151.1
    (36.5)
    151.5
    (42.5)
    161.4
    (51.0)
    153.6
    (43.3)
    155.5
    (44.9)
    Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    175.4
    (43.9)
    175.4
    (45.9)
    187.4
    (56.7)
    178.5
    (45.8)
    180.4
    (49.5)
    Apolipoprotein B Concentration (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    114.3
    (29.8)
    110.3
    (21.7)
    119.0
    (30.7)
    114.9
    (25.5)
    115.4
    (27.5)
    Total cholesterol/HDL-C Ratio (ratio) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [ratio]
    4.695
    (1.905)
    4.844
    (1.435)
    5.159
    (2.031)
    4.842
    (1.801)
    4.924
    (1.845)
    Apolipoprotein B/Apolipoprotein A1 Ratio (ratio) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [ratio]
    0.815
    (0.264)
    0.851
    (0.249)
    0.888
    (0.322)
    0.850
    (0.331)
    0.857
    (0.305)
    Lipoprotein(a) Concentration (nmol/L) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [nmol/L]
    44.0
    87.0
    77.5
    61.0
    65.0
    Triglyceride Concentration (mg/dL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [mg/dL]
    95.8
    102.0
    118.5
    112.5
    110.0
    Very Low-Density Lipoprotein Cholesterol (VLDL-C) Concentration (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    23.1
    (10.7)
    23.9
    (10.5)
    25.9
    (11.8)
    24.9
    (11.7)
    24.8
    (11.4)
    HDL-C Concentration (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    53.2
    (16.5)
    49.1
    (12.7)
    50.4
    (16.1)
    51.9
    (16.0)
    51.1
    (15.6)

    Outcome Measures

    1. Primary Outcome
    Title Percent 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. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.
    Arm/Group Title Placebo Q2W Placebo QM Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    -2.02
    (2.49)
    5.53
    (3.25)
    -61.25
    (1.77)
    -55.74
    (2.25)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments Within each dose frequency, the null hypothesis was that there was no mean difference in the percent change from baseline at week 12 or 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
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -59.23
    Confidence Interval (2-Sided) 95%
    -65.11 to -53.35
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.98
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments Within each dose frequency, the null hypothesis was that there was no mean difference in the percent change from baseline at week 12 or 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
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -61.27
    Confidence Interval (2-Sided) 95%
    -69.00 to -53.55
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.91
    Estimation Comments
    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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    -1.08
    (2.41)
    2.30
    (2.41)
    -61.23
    (1.71)
    -63.25
    (1.70)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments Within each dose frequency, the null hypothesis was that there was no mean difference in the percent change from baseline at week 12 or 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
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -60.15
    Confidence Interval (2-Sided) 95%
    -65.83 to -54.46
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.88
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments Within each dose frequency, the null hypothesis was that there was no mean difference in the percent change from baseline at week 12 or 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
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -65.55
    Confidence Interval (2-Sided) 95%
    -71.27 to -59.83
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.90
    Estimation Comments
    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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [mg/dL]
    -6.5
    (4.2)
    -1.3
    (4.1)
    -101.7
    (3.0)
    -98.8
    (2.9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -95.2
    Confidence Interval (2-Sided) 95%
    -105.1 to -85.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.0
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -97.4
    Confidence Interval (2-Sided) 95%
    -107.1 to -87.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.9
    Estimation Comments
    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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [mg/dL]
    -8.5
    (4.2)
    4.1
    (5.2)
    -101.3
    (3.0)
    -87.2
    (3.6)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -92.9
    Confidence Interval (2-Sided) 95%
    -102.9 to -82.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.1
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -91.3
    Confidence Interval (2-Sided) 95%
    -103.8 to -78.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.3
    Estimation Comments
    5. Secondary Outcome
    Title Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L)
    Description
    Time Frame Weeks 10 and 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Number (95% Confidence Interval) [percentage of participants]
    1.9
    3.5%
    1.9
    3.5%
    67.0
    60.4%
    80.4
    73.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 Cochran-Mantel Haenszel test stratified by baseline LDL-C and ezetimibe use.
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 65.1
    Confidence Interval (2-Sided) 95%
    52.8 to 73.4
    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
    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 Cochran-Mantel Haenszel test stratified by baseline LDL-C and ezetimibe use.
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 78.5
    Confidence Interval (2-Sided) 95%
    66.9 to 85.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12
    Description
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Number (95% Confidence Interval) [percentage of participants]
    2.0
    3.6%
    2.2
    4%
    68.3
    61.5%
    63.1
    57.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 Cochran-Mantel Haenszel test stratified by baseline LDL-C and ezetimibe use
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 66.3
    Confidence Interval (2-Sided) 95%
    53.7 to 74.6
    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
    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 Cochran-Mantel Haenszel test stratified by baseline LDL-C and ezetimibe use.
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 60.9
    Confidence Interval (2-Sided) 95%
    47.6 to 69.8
    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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    0.21
    (2.29)
    2.72
    (2.21)
    -55.79
    (1.63)
    -57.28
    (1.56)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -56.00
    Confidence Interval (2-Sided) 95%
    -61.41 to -50.59
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.74
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -60.01
    Confidence Interval (2-Sided) 95%
    -65.24 to -54.77
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.65
    Estimation Comments
    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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    -1.39
    (2.40)
    5.29
    (2.94)
    -56.19
    (1.71)
    -49.67
    (2.04)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -54.79
    Confidence Interval (2-Sided) 95%
    -60.47 to -49.12
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.87
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, 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%
    -61.95 to -47.96
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.54
    Estimation Comments
    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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    -0.19
    (2.10)
    2.21
    (1.97)
    -49.58
    (1.48)
    -52.76
    (1.36)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -49.39
    Confidence Interval (2-Sided) 95%
    -54.32 to -44.46
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.50
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -54.98
    Confidence Interval (2-Sided) 95%
    -59.58 to -50.38
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.33
    Estimation Comments
    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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    -0.67
    (2.32)
    4.60
    (2.70)
    -49.75
    (1.63)
    -44.81
    (1.80)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -49.09
    Confidence Interval (2-Sided) 95%
    -54.55 to -43.63
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.76
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -49.41
    Confidence Interval (2-Sided) 95%
    -55.73 to -43.10
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.19
    Estimation Comments
    11. Secondary Outcome
    Title Percent Change From Baseline in the Total Cholesterol/HDL-C 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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    0.86
    (2.05)
    4.14
    (2.13)
    -45.74
    (1.45)
    -45.02
    (1.50)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -46.59
    Confidence Interval (2-Sided) 95%
    -51.43 to -41.76
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.45
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -49.16
    Confidence Interval (2-Sided) 95%
    -54.21 to -44.11
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.56
    Estimation Comments
    12. Secondary Outcome
    Title Percent Change From Baseline in the Total Cholesterol/HDL-C 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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    0.12
    (2.19)
    7.11
    (3.13)
    -45.95
    (1.56)
    -38.32
    (2.15)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -46.08
    Confidence Interval (2-Sided) 95%
    -51.27 to -40.88
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.63
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -45.42
    Confidence Interval (2-Sided) 95%
    -52.86 to -37.98
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.77
    Estimation Comments
    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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    0.78
    (2.21)
    1.65
    (2.35)
    -52.39
    (1.56)
    -53.91
    (1.60)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -53.17
    Confidence Interval (2-Sided) 95%
    -58.35 to -47.99
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.62
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -55.56
    Confidence Interval (2-Sided) 95%
    -61.08 to -50.05
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.79
    Estimation Comments
    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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    1.54
    (2.49)
    4.23
    (3.66)
    -52.74
    (1.75)
    -45.31
    (2.42)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -54.28
    Confidence Interval (2-Sided) 95%
    -60.16 to -48.41
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.97
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -49.55
    Confidence Interval (2-Sided) 95%
    -58.14 to -40.96
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.35
    Estimation Comments
    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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    7.34
    (2.97)
    5.35
    (2.95)
    -24.03
    (2.09)
    -25.65
    (2.07)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -31.37
    Confidence Interval (2-Sided) 95%
    -38.33 to -24.41
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.52
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -31.00
    Confidence Interval (2-Sided) 95%
    -37.91 to -24.09
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.50
    Estimation Comments
    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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    8.68
    (3.27)
    6.69
    (3.16)
    -22.89
    (2.31)
    -21.55
    (2.17)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -31.57
    Confidence Interval (2-Sided) 95%
    -39.28 to -23.87
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.90
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -28.24
    Confidence Interval (2-Sided) 95%
    -35.61 to -20.88
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.73
    Estimation Comments
    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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    9.09
    (3.02)
    7.49
    (3.26)
    -13.27
    (2.14)
    -9.25
    (2.27)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -22.36
    Confidence Interval (2-Sided) 95%
    -29.48 to -15.24
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.60
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -16.74
    Confidence Interval (2-Sided) 95%
    -24.43 to -9.05
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.89
    Estimation Comments
    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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    3.50
    (3.51)
    6.43
    (4.15)
    -16.09
    (2.49)
    -5.13
    (2.84)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -19.59
    Confidence Interval (2-Sided) 95%
    -27.92 to -11.26
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.22
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -11.56
    Confidence Interval (2-Sided) 95%
    -21.38 to -1.74
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.97
    Estimation Comments
    19. Secondary Outcome
    Title Percent Change From Baseline in 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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    -0.45
    (1.70)
    -2.86
    (1.84)
    7.93
    (1.20)
    6.62
    (1.29)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 8.38
    Confidence Interval (2-Sided) 95%
    4.36 to 12.40
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.04
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 9.48
    Confidence Interval (2-Sided) 95%
    5.10 to 13.85
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.21
    Estimation Comments
    20. 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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    -1.15
    (1.91)
    -3.73
    (2.35)
    8.05
    (1.35)
    5.35
    (1.62)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 9.20
    Confidence Interval (2-Sided) 95%
    4.66 to 13.74
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.30
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 9.07
    Confidence Interval (2-Sided) 95%
    3.48 to 1466
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.83
    Estimation Comments
    21. 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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    8.66
    (2.90)
    6.34
    (3.27)
    -13.97
    (2.06)
    -9.20
    (2.27)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -22.63
    Confidence Interval (2-Sided) 95%
    -29.46 to -15.81
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.46
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -15.54
    Confidence Interval (2-Sided) 95%
    -23.25 to -7.84
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.90
    Estimation Comments
    22. 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
    Full analysis set
    Arm/Group Title Placebo Q2W Placebo QM Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 54 55 110 110
    Least Squares Mean (Standard Error) [percent change]
    3.73
    (3.50)
    4.10
    (4.17)
    -17.25
    (2.48)
    -5.06
    (2.84)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo Q2W, Evolocumab Q2W
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -20.97
    Confidence Interval (2-Sided) 95%
    -29.29 to -12.66
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.21
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo QM, Evolocumab QM
    Comments
    Type of Statistical Test Superiority or Other
    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 and ezetimibe use, scheduled visit, and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -9.17
    Confidence Interval (2-Sided) 95%
    -19.01 to 0.68
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.98
    Estimation Comments

    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 Evolocumab Q2W Evolocumab QM
    Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    All Cause Mortality
    Placebo Q2W Placebo QM Evolocumab Q2W Evolocumab QM
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo Q2W Placebo QM Evolocumab Q2W Evolocumab QM
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/54 (3.7%) 3/55 (5.5%) 3/110 (2.7%) 4/110 (3.6%)
    Cardiac disorders
    Acute myocardial infarction 0/54 (0%) 0/55 (0%) 1/110 (0.9%) 0/110 (0%)
    Angina pectoris 0/54 (0%) 0/55 (0%) 1/110 (0.9%) 1/110 (0.9%)
    Coronary artery disease 1/54 (1.9%) 0/55 (0%) 0/110 (0%) 0/110 (0%)
    Gastrointestinal disorders
    Inguinal hernia 1/54 (1.9%) 0/55 (0%) 0/110 (0%) 0/110 (0%)
    Pancreatitis acute 0/54 (0%) 0/55 (0%) 0/110 (0%) 1/110 (0.9%)
    Investigations
    Blood creatine phosphokinase increased 0/54 (0%) 1/55 (1.8%) 0/110 (0%) 0/110 (0%)
    Colonoscopy abnormal 0/54 (0%) 0/55 (0%) 0/110 (0%) 1/110 (0.9%)
    Endoscopy gastrointestinal abnormal 0/54 (0%) 0/55 (0%) 0/110 (0%) 1/110 (0.9%)
    Nervous system disorders
    Epilepsy 0/54 (0%) 0/55 (0%) 0/110 (0%) 1/110 (0.9%)
    Psychiatric disorders
    Depression 0/54 (0%) 1/55 (1.8%) 0/110 (0%) 0/110 (0%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/54 (0%) 1/55 (1.8%) 0/110 (0%) 0/110 (0%)
    Skin and subcutaneous tissue disorders
    Erythema 0/54 (0%) 0/55 (0%) 1/110 (0.9%) 0/110 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo Q2W Placebo QM Evolocumab Q2W Evolocumab QM
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/54 (9.3%) 10/55 (18.2%) 17/110 (15.5%) 24/110 (21.8%)
    Infections and infestations
    Nasopharyngitis 2/54 (3.7%) 3/55 (5.5%) 8/110 (7.3%) 11/110 (10%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/54 (1.9%) 1/55 (1.8%) 7/110 (6.4%) 1/110 (0.9%)
    Back pain 0/54 (0%) 1/55 (1.8%) 2/110 (1.8%) 6/110 (5.5%)
    Nervous system disorders
    Dizziness 1/54 (1.9%) 3/55 (5.5%) 0/110 (0%) 4/110 (3.6%)
    Headache 1/54 (1.9%) 3/55 (5.5%) 4/110 (3.6%) 5/110 (4.5%)

    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:
    NCT01763918
    Other Study ID Numbers:
    • 20110117
    • 2012-001365-32
    First Posted:
    Jan 9, 2013
    Last Update Posted:
    Jun 17, 2019
    Last Verified:
    Jun 1, 2019