Clincosm LogoSign in Get a demo

LAPLACE-2: LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy-2

Sponsor
Amgen (Industry)
Overall Status
Completed
CT.gov ID
NCT01763866
Collaborator
(none)
2,067
Enrollment
244
Locations
24
Arms
10.6
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 administered subcutaneously every 2 weeks (Q2W) and monthly (QM) when used in combination with a statin, compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in patients with primary hypercholesterolemia and mixed dyslipidemia.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Prior to the first randomization, participants entered a screening period to determine eligibility. During screening, all participants received subcutaneous placebo corresponding to the once monthly dose volume. Participants who completed the screening period and met eligibility criteria were randomized to 1 of 5 open-label statin cohorts (atorvastatin 10 mg or 80 mg, rosuvastatin 5 mg or 40 mg, or simvastatin 40 mg) for a 4 week lipid stabilization period based on statin therapy at the time of study entry (no statin use vs non-intensive statin use vs intensive statin use).

After the 4-week lipid-stabilization period, eligible patients taking rosuvastatin or simvastatin during the lipid-stabilization phase were then randomized to 1 of 4 treatment groups: evolocumab (140 mg, subcutaneous, every 2 weeks) or matching placebo (subcutaneous, every 2 weeks), or evolocumab (420 mg, subcutaneous, monthly) or matching placebo (subcutaneous, monthly). Patients taking atorvastatin during the lipid-stabilization phase were then randomized to 1 of 6 treatment groups: evolocumab (140 mg, subcutaneous, every 2 weeks) and placebo (oral, daily), evolocumab (420 mg, subcutaneous, monthly) and placebo (oral, daily), placebo (subcutaneous, every 2 weeks) and placebo (oral, daily) or ezetimibe (10 mg, oral, daily), or placebo (subcutaneous, monthly) and placebo (oral, daily) or ezetimibe (10 mg, oral, daily).

A participant was considered randomized into the study after successfully completing the screening period, meeting all inclusion/exclusion criteria, and undergoing both randomization procedures.

Participants randomized to simvastatin who were taking verapamil or diltiazem prior to randomization received simvastatin 10 mg once daily (QD) while participants who were taking amlodipine, amiodarone or ranolazine prior to randomization received simvastatin 20 mg QD. All other participants randomized to simvastatin received simvastatin 40 mg QD.

Study Design

Study Type:
Interventional
Actual Enrollment :
2067 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, Tolerability and Efficacy of AMG 145 on LDL-C in Combination With Statin Therapy in Subjects With Primary Hypercholesterolemia and Mixed Dyslipidemia
Actual Study Start Date :
Jan 15, 2013
Actual Primary Completion Date :
Nov 12, 2013
Actual Study Completion Date :
Dec 4, 2013

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: A10 PBO Q2W

Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks.

Drug: Placebo to Evolocumab
Administered by subcutaneous injection

Drug: Placebo to Ezetimibe
Administered orally once a day

Drug: Atorvastatin
Administered orally once a day
Other Names:
  • Lipitor

    		•
    Placebo Comparator: A10 PBO QM

    Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.

    Drug: Placebo to Evolocumab
    Administered by subcutaneous injection

    Drug: Placebo to Ezetimibe
    Administered orally once a day

    Drug: Atorvastatin
    Administered orally once a day
    Other Names:
  • Lipitor

    		•
    Active Comparator: A10 EZE (Q2W)

    Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once a day for up to 12 weeks.

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

    • Drug: Placebo to Evolocumab
    Administered by subcutaneous injection

    Drug: Atorvastatin
    Administered orally once a day
    Other Names:
  • Lipitor

    		•
    Active Comparator: A10 EZE (QM)

    Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with 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

    • Drug: Placebo to Evolocumab
    Administered by subcutaneous injection

    Drug: Atorvastatin
    Administered orally once a day
    Other Names:
  • Lipitor

    		•
    Experimental: A10 EvoMab Q2W

    Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with 140 mg evolocumab (EvoMab) 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

    • Drug: Placebo to Ezetimibe
    Administered orally once a day

    Drug: Atorvastatin
    Administered orally once a day
    Other Names:
  • Lipitor

    		•
    Experimental: A10 EvoMab QM

    Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then with 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

    • Drug: Placebo to Ezetimibe
    Administered orally once a day

    Drug: Atorvastatin
    Administered orally once a day
    Other Names:
  • Lipitor

    		•
    Placebo Comparator: A80 PBO Q2W

    Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.

    Drug: Placebo to Evolocumab
    Administered by subcutaneous injection

    Drug: Placebo to Ezetimibe
    Administered orally once a day

    Drug: Atorvastatin
    Administered orally once a day
    Other Names:
  • Lipitor

    		•
    Placebo Comparator: A80 PBO QM

    Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month and placebo tablets once a day for up to 12 weeks.

    Drug: Placebo to Evolocumab
    Administered by subcutaneous injection

    Drug: Placebo to Ezetimibe
    Administered orally once a day

    Drug: Atorvastatin
    Administered orally once a day
    Other Names:
  • Lipitor

    		•
    Active Comparator: A80 EZE (Q2W)

    Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with 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

    • Drug: Placebo to Evolocumab
    Administered by subcutaneous injection

    Drug: Atorvastatin
    Administered orally once a day
    Other Names:
  • Lipitor

    		•
    Active Comparator: A80 EZE (QM)

    Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with 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

    • Drug: Placebo to Evolocumab
    Administered by subcutaneous injection

    Drug: Atorvastatin
    Administered orally once a day
    Other Names:
  • Lipitor

    		•
    Experimental: A80 EvoMab Q2W

    Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with 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

    • Drug: Placebo to Ezetimibe
    Administered orally once a day

    Drug: Atorvastatin
    Administered orally once a day
    Other Names:
  • Lipitor

    		•
    Experimental: A80 EvoMab QM

    Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then with 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

    • Drug: Placebo to Ezetimibe
    Administered orally once a day

    Drug: Atorvastatin
    Administered orally once a day
    Other Names:
  • Lipitor

    		•
    Placebo Comparator: R5 PBO Q2W

    Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.

    Drug: Placebo to Evolocumab
    Administered by subcutaneous injection

    Drug: Rosuvastatin
    Administered orally once a day
    Other Names:
  • Crestor

    		•
    Placebo Comparator: R5 PBO QM

    Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month for up to 12 weeks.

    Drug: Placebo to Evolocumab
    Administered by subcutaneous injection

    Drug: Rosuvastatin
    Administered orally once a day
    Other Names:
  • Crestor

    		•
    Experimental: R5 EvoMab Q2W

    Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with 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

    • Drug: Rosuvastatin
    Administered orally once a day
    Other Names:
  • Crestor

    		•
    Experimental: R5 EvoMab QM

    Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then with 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

    • Drug: Rosuvastatin
    Administered orally once a day
    Other Names:
  • Crestor

    		•
    Placebo Comparator: R40 PBO Q2W

    Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.

    Drug: Placebo to Evolocumab
    Administered by subcutaneous injection

    Drug: Rosuvastatin
    Administered orally once a day
    Other Names:
  • Crestor

    		•
    Placebo Comparator: R40 PBO QM

    Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month for up to 12 weeks.

    Drug: Placebo to Evolocumab
    Administered by subcutaneous injection

    Drug: Rosuvastatin
    Administered orally once a day
    Other Names:
  • Crestor

    		•
    Experimental: R40 EvoMab Q2W

    Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with 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

    • Drug: Rosuvastatin
    Administered orally once a day
    Other Names:
  • Crestor

    		•
    Experimental: R40 EvoMab QM

    Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then with 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

    • Drug: Rosuvastatin
    Administered orally once a day
    Other Names:
  • Crestor

    		•
    Placebo Comparator: S40 PBO Q2W

    Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every 2 weeks for up to 12 weeks.

    Drug: Placebo to Evolocumab
    Administered by subcutaneous injection

    Drug: Simvastatin
    Administered orally once a day
    Other Names:
  • Zocor

    		•
    Placebo Comparator: S40 PBO QM

    Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with placebo subcutaneous injection once every month for up to 12 weeks.

    Drug: Placebo to Evolocumab
    Administered by subcutaneous injection

    Drug: Simvastatin
    Administered orally once a day
    Other Names:
  • Zocor

    		•
    Experimental: S40 EvoMab Q2W

    Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with 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

    • Drug: Simvastatin
    Administered orally once a day
    Other Names:
  • Zocor

    		•
    Experimental: S40 EvoMab QM

    Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then with 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

    • Drug: Simvastatin
    Administered orally once a day
    Other Names:
  • Zocor

    		•

    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 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. 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]

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

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

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

    7. 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]

    8. Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 [Baseline and Week 12]

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

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

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

    12. Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 [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 Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12 [Baseline and Weeks 10 and 12]

    18. Percent Change From Baseline in Very Low-Density Cholesterol (VLDL-C) at Week 12 [Baseline and Week 12]

    19. Percent Change From Baseline in 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

    • Subjects not taking a statin must have fasting LDL-C of at least 150 mg/dL (4.0 mmol/L)

    • Subjects already on a non-intensive statin must have fasting LDL-C at screening ≥ 100 mg/dL (2.6 mmol/L)

    • Subjects already on a intensive statin must have fasting LDL-C at screening ≥ 80 mg/dL (2.1 mmol/L)

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

    Exclusion Criteria:

    • Statin intolerance

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

    • Uncontrolled hypertension

    • Uncontrolled cardiac arrhythmia

    • 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 35294
    2 Research Site Glendale Arizona United States 85306
    3 Research Site Tucson Arizona United States 85710
    4 Research Site Tucson Arizona United States 85712
    5 Research Site Carmichael California United States 95608
    6 Research Site Encino California United States 91436
    7 Research Site Long Beach California United States 90822
    8 Research Site Newport Beach California United States 92663
    9 Research Site San Diego California United States 92123
    10 Research Site Santa Ana California United States 92705
    11 Research Site Santa Rosa California United States 95405
    12 Research Site Thousand Oaks California United States 91360
    13 Research Site Torrance California United States 90509
    14 Research Site Tustin California United States 92780
    15 Research Site Westlake Village California United States 91361
    16 Research Site Littleton Colorado United States 80120
    17 Research Site Daytona Beach Florida United States 32117
    18 Research Site Jacksonville Florida United States 32223
    19 Research Site Melbourne Florida United States 32901
    20 Research Site Miami Florida United States 33173
    21 Research Site Port Charlotte Florida United States 33952
    22 Research Site Atlanta Georgia United States 30328
    23 Research Site Atlanta Georgia United States 30342
    24 Research Site Boise Idaho United States 83704
    25 Research Site Hammond Indiana United States 46320
    26 Research Site Indianapolis Indiana United States 46237
    27 Research Site Valparaiso Indiana United States 46383
    28 Research Site Iowa City Iowa United States 52242
    29 Research Site Crestview Hills Kentucky United States 41017
    30 Research Site Monroe Louisiana United States 71203
    31 Research Site Auburn Maine United States 04210
    32 Research Site Bangor Maine United States 04401
    33 Research Site Portland Maine United States 04101
    34 Research Site Baltimore Maryland United States 21201
    35 Research Site Ypsilanti Michigan United States 48197
    36 Research Site Tupelo Mississippi United States 38801
    37 Research Site Billings Montana United States 59102
    38 Research Site Voorhees New Jersey United States 08043
    39 Research Site Manlius New York United States 13104
    40 Research Site Rochester New York United States 14609
    41 Research Site Syracuse New York United States 13210
    42 Research Site Williamsville New York United States 14221
    43 Research Site Winston-Salem North Carolina United States 27103
    44 Research Site Cadiz Ohio United States 43907
    45 Research Site Canton Ohio United States 44708
    46 Research Site Cincinnati Ohio United States 45219
    47 Research Site Cincinnati Ohio United States 45227
    48 Research Site Dayton Ohio United States 45414
    49 Research Site Mansfield Ohio United States 44906
    50 Research Site Marion Ohio United States 43302
    51 Research Site Sandusky Ohio United States 44870
    52 Research Site Norman Oklahoma United States 73069
    53 Research Site Duncansville Pennsylvania United States 16635
    54 Research Site Pittsburgh Pennsylvania United States 15216
    55 Research Site York Pennsylvania United States 17405
    56 Research Site Florence South Carolina United States 29501
    57 Research Site Rapid City South Dakota United States 57701
    58 Research Site Jackson Tennessee United States 38301
    59 Research Site Jackson Tennessee United States 38305
    60 Research Site Dallas Texas United States 75231
    61 Research Site Houston Texas United States 77074
    62 Research Site San Antonio Texas United States 78229
    63 Research Site Suffolk Virginia United States 23435
    64 Research Site Winchester Virginia United States 22601
    65 Research Site Tacoma Washington United States 98405
    66 Research Site Sydney New South Wales Australia 2022
    67 Research Site Ashford South Australia Australia 5035
    68 Research Site Fullarton South Australia Australia 5063
    69 Research Site Fitzroy Victoria Australia 3065
    70 Research Site Heidelberg Heights Victoria Australia 3081
    71 Research Site Richmond Victoria Australia 3121
    72 Research Site Blankenberge Belgium 8370
    73 Research Site Chênée Belgium 4032
    74 Research Site Hasselt Belgium 3500
    75 Research Site Oostende Belgium 8400
    76 Research Site Tremelo Belgium 3120
    77 Research Site Vilvoorde Belgium 1800
    78 Research Site Burnaby British Columbia Canada V5G 1T4
    79 Research Site Kelowna British Columbia Canada V1Y 1E4
    80 Research Site Kelowna British Columbia Canada V1Y 1V6
    81 Research Site Surrey British Columbia Canada V3V 1N1
    82 Research Site Saint John’s Newfoundland and Labrador Canada A1A 3R5
    83 Research Site Cambridge Ontario Canada N1R 6V6
    84 Research Site Hamilton Ontario Canada L8L 2X2
    85 Research Site London Ontario Canada N5W 6A2
    86 Research Site Newmarket Ontario Canada L3Y 5G8
    87 Research Site Oshawa Ontario Canada L1J 2K1
    88 Research Site Sarnia Ontario Canada N7T 4X3
    89 Research Site Scarborough Ontario Canada M1P 2T7
    90 Research Site Toronto Ontario Canada M8V 3X8
    91 Research Site Toronto Ontario Canada M9V 4B4
    92 Research Site Woodstock Ontario Canada N4S 5P5
    93 Research Site Brossard Quebec Canada J4X 1S4
    94 Research Site Greenfield Park Quebec Canada J4V 2G8
    95 Research Site Lachine Quebec Canada H8S 2E4
    96 Research Site Longueuil Quebec Canada J4N 0C9
    97 Research Site Montreal Quebec Canada H4N 2W2
    98 Research Site Pointe-Claire Quebec Canada H9R 3J1
    99 Research Site Brno Czechia 602 00
    100 Research Site Brno Czechia 603 00
    101 Research Site Kladno Czechia 272 01
    102 Research Site Litomerice Czechia 412 01
    103 Research Site Moravske Budejovice Czechia 676 02
    104 Research Site Olomouc Czechia 775 20
    105 Research Site Pardubice Czechia 530 02
    106 Research Site Praha 2 Czechia 120 00
    107 Research Site Praha 3 Czechia 130 00
    108 Research Site Praha 4 Czechia 140 21
    109 Research Site Slany Czechia 274 01
    110 Research Site Svitavy Czechia 568 25
    111 Research Site Usti nad Orlici Czechia 562 18
    112 Research Site Aalborg Denmark 9000
    113 Research Site Ballerup Denmark 2750
    114 Research Site Vejle Denmark 7100
    115 Research Site Brest Cedex 2 France 29200
    116 Research Site Caen Cedex 9 France 14033
    117 Research Site Dijon France 21034
    118 Research Site Le Creusot France 71200
    119 Research Site Montpellier cedex 05 France 34295
    120 Research Site Nantes Cedex 1 France 44093
    121 Research Site Paris cedex 12 France 75571
    122 Research Site Paris France 75013
    123 Research Site Poitiers France 86000
    124 Research Site Strasbourg France 67091
    125 Research Site Bad Krozingen Germany 79189
    126 Research Site Berlin (Hellersdorf) Germany 12627
    127 Research Site Berlin Germany 10367
    128 Research Site Berlin Germany 10787
    129 Research Site Freiburg Germany 79106
    130 Research Site Heidelberg Germany 69120
    131 Research Site Homburg Germany 66421
    132 Research Site Leipzig Germany 04103
    133 Research Site Magdeburg Germany 39104
    134 Research Site Messkirch Germany 88605
    135 Research Site Witten Germany 58455
    136 Research Site Hong Kong Hong Kong
    137 Research Site New Territories Hong Kong
    138 Research Site Baja Hungary 6500
    139 Research Site Berettyoujfalu Hungary 4100
    140 Research Site Dunaujvaros Hungary 2400
    141 Research Site Eger Hungary 3300
    142 Research Site Gyongyos Hungary 3200
    143 Research Site Hodmezovasarhely Hungary 6800
    144 Research Site Jaszbereny Hungary 5100
    145 Research Site Komarom Hungary 2921
    146 Research Site Marcali Hungary 8700
    147 Research Site Mosonmagyarovar Hungary 9200
    148 Research Site Pecs Hungary 7624
    149 Research Site Bologna Italy 40138
    150 Research Site Cagliari Italy 09134
    151 Research Site Chieti Italy 66100
    152 Research Site Ferrara Italy 44124
    153 Research Site Milano Italy 20162
    154 Research Site Napoli Italy 80131
    155 Research Site Padova Italy 35128
    156 Research Site Perugia Italy 06129
    157 Research Site Pisa Italy 56124
    158 Research Site Trieste Italy 34149
    159 Research Site Seoul Korea, Republic of 120-752
    160 Research Site Seoul Korea, Republic of 135-710
    161 Research Site Seoul Korea, Republic of 138-736
    162 Research Site Suwon-si Korea, Republic of 443-380
    163 Research Site Suwon Korea, Republic of 443-721
    164 Research Site Mexico Distrito Federal Mexico 03800
    165 Research Site Mexico Distrito Federal Mexico 14000
    166 Research Site Leon Guanajuato Mexico 37520
    167 Research Site Guadalajara Jalisco Mexico 44100
    168 Research Site Guadalajara Jalisco Mexico 44130
    169 Research Site Monterrey Nuevo León Mexico 64460
    170 Research Site San Luis Potosi San Luis PotosÃ- Mexico 78240
    171 Research Site Tampico Tamaulipas Mexico 89000
    172 Research Site Durango Mexico 34270
    173 Research Site Amsterdam Netherlands 1066 EC
    174 Research Site Amsterdam Netherlands 1105 AZ
    175 Research Site Den Helder Netherlands 1782 GZ
    176 Research Site Groningen Netherlands 9728 NT
    177 Research Site Hoogeveen Netherlands 7909 AA
    178 Research Site Nieuwegein Netherlands 3435 CM
    179 Research Site Nijmegen Netherlands 6525 GA
    180 Research Site Rotterdam Netherlands 3045 PM
    181 Research Site Waalwijk Netherlands 5141 BM
    182 Research Site Zwijndrecht Netherlands 3331 LZ
    183 Research Site Barnaul Russian Federation 656055
    184 Research Site Kemerovo Russian Federation 650002
    185 Research Site Moscow Russian Federation 121002
    186 Research Site Moscow Russian Federation 121552
    187 Research Site Moscow Russian Federation 127299
    188 Research Site Novosibirsk Russian Federation 630047
    189 Research Site Saint Petersburg Russian Federation 192242
    190 Research Site Saint Petersburg Russian Federation 197022
    191 Research Site Saint Petersburg Russian Federation 197341
    192 Research Site Saint-Petersburg Russian Federation 194156
    193 Research Site Saratov Russian Federation 410054
    194 Research Site Alberton Gauteng South Africa 1449
    195 Research Site Johannesburg Gauteng South Africa 2196
    196 Research Site Lyttelton Gauteng South Africa 0140
    197 Research Site Pretoria Gauteng South Africa 0184
    198 Research Site Kuils River Western Cape South Africa 7580
    199 Research Site Somerset West Western Cape South Africa 7130
    200 Research Site Bloemfontein South Africa 9301
    201 Research Site Cape Town South Africa 7405
    202 Research Site Almeria AndalucÃ-a Spain 04001
    203 Research Site AlmerÃ-a AndalucÃ-a Spain 04001
    204 Research Site Barcelona Cataluña Spain 08003
    205 Research Site Barcelona Cataluña Spain 08036
    206 Research Site L'Hospitalet de Llobregat Cataluña Spain 08907
    207 Research Site Valencia Comunidad Valenciana Spain 46010
    208 Research Site Pozuelo de Alarcon Madrid Spain 28223
    209 Research Site Pozuelo De Alarcón Madrid Spain 28223
    210 Research Site Madrid Spain 28007
    211 Research Site Madrid Spain 28029
    212 Research Site Göteborg Sweden 413 45
    213 Research Site Lund Sweden 222 21
    214 Research Site Lund Sweden 222 22
    215 Research Site Stockholm Sweden 171 45
    216 Research Site Uddevalla Sweden 451 50
    217 Research Site Ã-rebro Sweden 701 46
    218 Research Site Bellinzona Switzerland 6500
    219 Research Site Geneva 14 Switzerland 1211
    220 Research Site Lausanne Switzerland 1011
    221 Research Site Muensterlingen Switzerland 8596
    222 Research Site St. Gallen Switzerland 9007
    223 Research Site Zurich Switzerland 8063
    224 Research Site Kaohsiung Taiwan 807
    225 Research Site Kaohsiung Taiwan 83301
    226 Research Site Taipei Taiwan 100
    227 Research Site Birmingham United Kingdom B15 2SQ
    228 Research Site Blackpool United Kingdom FY3 7EN
    229 Research Site Cardiff United Kingdom CF14 5GJ
    230 Research Site Chesterfield United Kingdom S40 4TF
    231 Research Site Chorley United Kingdom PR7 7NA
    232 Research Site Doncaster United Kingdom DN9 1EP
    233 Research Site Glasgow United Kingdom G20 0SP
    234 Research Site Glasgow United Kingdom G45 9AW
    235 Research Site Harrow United Kingdom HA3 7LT
    236 Research Site Liverpool United Kingdom L22 0LG
    237 Research Site Liverpool United Kingdom L7 8XP
    238 Research Site Manchester United Kingdom M13 9WL
    239 Research Site Manchester United Kingdom M15 6SX
    240 Research Site Reading United Kingdom RG2 0FT
    241 Research Site Reading United Kingdom RG2 0TG
    242 Research Site Scunthorpe United Kingdom DN15 7BH
    243 Research Site Wakefield United Kingdom WF1 4DG
    244 Research Site Whitby United Kingdom YO21 1SD

    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:
    NCT01763866
    Other Study ID Numbers:
    • 20110115
    • 2012-001363-70
    First Posted:
    Jan 9, 2013
    Last Update Posted:
    Jan 14, 2021
    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
    Atorvastatin
    Rosuvastatin Calcium
    Simvastatin
    Ezetimibe
    Evolocumab
    Antibodies, Monoclonal

    Study Results

    Participant Flow

    Recruitment Details Adults aged 18 to 80 years with screening low-density lipoprotein cholesterol (LDL-C) ≥ 150 mg/dL (no statin at screening), ≥ 100 mg/dL (non-intensive statin at screening), or ≥ 80 mg/dL (intensive statin at screening) and fasting triglycerides ≤ 400 mg/dL. First patient enrolled on 15 January 2013; Last patient enrolled on 10 July 2013.
    Pre-assignment Detail 2067 patients were first randomized to 1 of the 5 open-label statin cohorts (atorvastatin 10 mg or 80 mg, rosuvastatin 5 mg or 40 mg, or simvastatin 40 mg); 1899 were then randomized to blinded investigational product. Randomization into the statin dose cohorts was stratified by entry statin therapy and by use of certain concomitant medications.
    Arm/Group Title A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Period Title: Overall Study
    STARTED 56 55 56 55 110 110 55 55 56 54 110 110 58 57 114 115 56 56 111 112 56 55 112 115
    Received Treatment 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    COMPLETED 54 54 51 55 108 107 48 55 53 53 102 108 54 57 102 112 55 55 105 110 52 54 109 113
    NOT COMPLETED 2 1 5 0 2 3 7 0 3 1 8 2 4 0 12 3 1 1 6 2 4 1 3 2

    Baseline Characteristics

    Arm/Group Title A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM Total
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Total of all reporting groups
    Overall Participants 56 55 56 55 110 110 55 55 56 54 110 110 58 57 114 115 56 56 111 112 56 55 112 115 1899
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.3
    (10.5)
    62.2
    (10.4)
    61.0
    (9.0)
    60.6
    (9.2)
    58.3
    (8.4)
    59.6
    (11.1)
    57.1
    (9.9)
    58.8
    (11.5)
    60.5
    (10.2)
    61.1
    (8.9)
    59.7
    (10.2)
    60.1
    (10.2)
    61.2
    (9.1)
    59.6
    (9.2)
    58.9
    (11.2)
    59.3
    (10.5)
    60.2
    (8.7)
    58.3
    (11.3)
    59.5
    (9.2)
    59.6
    (9.0)
    61.9
    (9.7)
    61.5
    (10.3)
    59.7
    (9.2)
    61.5
    (9.6)
    59.8
    (9.9)
    Sex: Female, Male (Count of Participants)
    Female
    24
    42.9%
    28
    50.9%
    29
    51.8%
    28
    50.9%
    56
    50.9%
    44
    40%
    22
    40%
    24
    43.6%
    24
    42.9%
    28
    51.9%
    44
    40%
    48
    43.6%
    35
    60.3%
    27
    47.4%
    52
    45.6%
    51
    44.3%
    21
    37.5%
    27
    48.2%
    43
    38.7%
    52
    46.4%
    32
    57.1%
    28
    50.9%
    45
    40.2%
    59
    51.3%
    871
    45.9%
    Male
    32
    57.1%
    27
    49.1%
    27
    48.2%
    27
    49.1%
    54
    49.1%
    66
    60%
    33
    60%
    31
    56.4%
    32
    57.1%
    26
    48.1%
    66
    60%
    62
    56.4%
    23
    39.7%
    30
    52.6%
    62
    54.4%
    64
    55.7%
    35
    62.5%
    29
    51.8%
    68
    61.3%
    60
    53.6%
    24
    42.9%
    27
    49.1%
    67
    59.8%
    56
    48.7%
    1028
    54.1%
    Race/Ethnicity, Customized (participants) [Number]
    Hispanic or Latino
    3
    5.4%
    2
    3.6%
    2
    3.6%
    1
    1.8%
    5
    4.5%
    2
    1.8%
    5
    9.1%
    5
    9.1%
    4
    7.1%
    4
    7.4%
    5
    4.5%
    7
    6.4%
    2
    3.4%
    4
    7%
    6
    5.3%
    3
    2.6%
    2
    3.6%
    3
    5.4%
    6
    5.4%
    5
    4.5%
    1
    1.8%
    2
    3.6%
    3
    2.7%
    5
    4.3%
    87
    4.6%
    Not Hispanic or Latino
    53
    94.6%
    53
    96.4%
    54
    96.4%
    54
    98.2%
    105
    95.5%
    108
    98.2%
    50
    90.9%
    50
    90.9%
    52
    92.9%
    50
    92.6%
    105
    95.5%
    103
    93.6%
    56
    96.6%
    53
    93%
    108
    94.7%
    112
    97.4%
    54
    96.4%
    53
    94.6%
    105
    94.6%
    107
    95.5%
    55
    98.2%
    53
    96.4%
    109
    97.3%
    110
    95.7%
    1812
    95.4%
    Race/Ethnicity, Customized (participants) [Number]
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    0
    0%
    1
    0.1%
    Asian
    1
    1.8%
    0
    0%
    2
    3.6%
    1
    1.8%
    3
    2.7%
    4
    3.6%
    1
    1.8%
    0
    0%
    0
    0%
    3
    5.6%
    1
    0.9%
    1
    0.9%
    0
    0%
    0
    0%
    2
    1.8%
    1
    0.9%
    1
    1.8%
    0
    0%
    0
    0%
    0
    0%
    3
    5.4%
    0
    0%
    1
    0.9%
    0
    0%
    25
    1.3%
    Black or African American
    3
    5.4%
    0
    0%
    1
    1.8%
    2
    3.6%
    9
    8.2%
    4
    3.6%
    1
    1.8%
    2
    3.6%
    3
    5.4%
    4
    7.4%
    3
    2.7%
    4
    3.6%
    2
    3.4%
    1
    1.8%
    7
    6.1%
    5
    4.3%
    0
    0%
    3
    5.4%
    5
    4.5%
    3
    2.7%
    3
    5.4%
    1
    1.8%
    4
    3.6%
    5
    4.3%
    75
    3.9%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.8%
    0
    0%
    1
    1.9%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.8%
    0
    0%
    0
    0%
    0
    0%
    4
    0.2%
    White
    52
    92.9%
    55
    100%
    53
    94.6%
    52
    94.5%
    97
    88.2%
    101
    91.8%
    51
    92.7%
    52
    94.5%
    53
    94.6%
    46
    85.2%
    105
    95.5%
    105
    95.5%
    56
    96.6%
    56
    98.2%
    104
    91.2%
    107
    93%
    55
    98.2%
    52
    92.9%
    105
    94.6%
    109
    97.3%
    49
    87.5%
    54
    98.2%
    106
    94.6%
    110
    95.7%
    1785
    94%
    Other
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    0
    0%
    2
    3.6%
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    1
    0.9%
    0
    0%
    1
    1.8%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    7
    0.4%
    Mixed Race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    0.1%
    Stratification Factor: Entry Statin Therapy (participants) [Number]
    Intensive statin use
    18
    32.1%
    19
    34.5%
    10
    17.9%
    14
    25.5%
    28
    25.5%
    35
    31.8%
    15
    27.3%
    12
    21.8%
    21
    37.5%
    11
    20.4%
    34
    30.9%
    35
    31.8%
    13
    22.4%
    13
    22.8%
    33
    28.9%
    38
    33%
    13
    23.2%
    13
    23.2%
    33
    29.7%
    37
    33%
    19
    33.9%
    13
    23.6%
    31
    27.7%
    34
    29.6%
    542
    28.5%
    Non-intensive statin use
    20
    35.7%
    25
    45.5%
    30
    53.6%
    21
    38.2%
    52
    47.3%
    40
    36.4%
    22
    40%
    27
    49.1%
    22
    39.3%
    21
    38.9%
    47
    42.7%
    46
    41.8%
    25
    43.1%
    28
    49.1%
    49
    43%
    42
    36.5%
    23
    41.1%
    22
    39.3%
    50
    45%
    44
    39.3%
    21
    37.5%
    26
    47.3%
    45
    40.2%
    48
    41.7%
    796
    41.9%
    No statin use
    18
    32.1%
    11
    20%
    16
    28.6%
    20
    36.4%
    30
    27.3%
    35
    31.8%
    18
    32.7%
    16
    29.1%
    13
    23.2%
    22
    40.7%
    29
    26.4%
    29
    26.4%
    20
    34.5%
    16
    28.1%
    32
    28.1%
    35
    30.4%
    20
    35.7%
    21
    37.5%
    28
    25.2%
    31
    27.7%
    16
    28.6%
    16
    29.1%
    36
    32.1%
    33
    28.7%
    561
    29.5%
    Low-Density Lipoprotein Cholesterol (LDL-C) Concentration (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    123.0
    (46.6)
    123.7
    (47.9)
    126.8
    (49.6)
    119.3
    (28.1)
    124.2
    (43.4)
    126.1
    (50.4)
    100.3
    (36.2)
    94.7
    (31.9)
    98.7
    (34.0)
    92.3
    (19.3)
    94.2
    (34.8)
    93.8
    (32.3)
    115.6
    (39.8)
    119.9
    (39.1)
    118.7
    (40.9)
    122.9
    (42.0)
    77.4
    (20.9)
    102.9
    (49.3)
    88.5
    (31.5)
    88.5
    (31.3)
    110.3
    (28.0)
    108.6
    (30.9)
    114.9
    (34.5)
    123.7
    (48.5)
    109.1
    (41.1)
    Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    149.1
    (46.9)
    147.7
    (51.4)
    153.8
    (53.2)
    148.3
    (36.8)
    152.3
    (45.6)
    154.3
    (53.1)
    124.2
    (39.3)
    116.5
    (35.7)
    124.8
    (35.4)
    118.4
    (25.5)
    120.2
    (42.3)
    117.2
    (36.3)
    141.1
    (41.6)
    148.3
    (43.3)
    146.6
    (43.2)
    152.0
    (46.4)
    103.9
    (25.7)
    128.7
    (53.4)
    113.5
    (36.0)
    114.3
    (34.7)
    138.4
    (29.3)
    135.7
    (38.4)
    146.8
    (41.8)
    151.2
    (51.5)
    150.3
    (27.6)
    Apolipoprotein B Concentration (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    95.3
    (26.0)
    95.3
    (29.6)
    101.3
    (31.2)
    94.6
    (20.4)
    99.7
    (26.4)
    97.3
    (28.9)
    81.1
    (22.1)
    80.1
    (21.4)
    85.3
    (23.1)
    78.7
    (16.9)
    79.9
    (25.1)
    77.9
    (21.5)
    93.1
    (27.3)
    95.9
    (25.2)
    95.4
    (27.0)
    97.2
    (26.9)
    71.0
    (16.6)
    84.8
    (29.7)
    77.4
    (22.3)
    78.7
    (23.1)
    91.6
    (18.4)
    89.8
    (20.7)
    94.2
    (24.0)
    96.5
    (27.5)
    89.1
    (26.1)
    Total Cholesterol/HDL-C Ratio (ratio) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [ratio]
    3.988
    (1.154)
    3.859
    (1.396)
    4.112
    (1.311)
    4.002
    (1.100)
    3.980
    (1.224)
    4.100
    (1.636)
    3.704
    (1.260)
    3.461
    (1.093)
    3.748
    (1.099)
    3.540
    (1.100)
    3.696
    (1.371)
    3.462
    (1.000)
    4.044
    (1.685)
    3.891
    (1.234)
    3.915
    (1.216)
    4.178
    (1.932)
    3.086
    (0.728)
    3.547
    (1.355)
    3.413
    (1.355)
    3.307
    (1.061)
    3.733
    (1.079)
    3.595
    (1.345)
    4.196
    (1.436)
    3.924
    (1.420)
    3.786
    (1.353)
    Apolipoprotein B/Apolipoprotein A1 Ratio (ratio) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [ratio]
    0.666
    (0.216)
    0.647
    (0.266)
    0.692
    (0.243)
    0.640
    (0.169)
    0.663
    (0.217)
    0.659
    (0.249)
    0.603
    (0.221)
    0.571
    (0.189)
    0.640
    (0.234)
    0.560
    (0.157)
    0.593
    (0.227)
    0.562
    (0.171)
    0.661
    (0.273)
    0.636
    (0.207)
    0.640
    (0.249)
    0.676
    (0.341)
    0.479
    (0.129)
    0.562
    (0.217)
    0.538
    (0.227)
    0.536
    (0.193)
    0.611
    (0.179)
    0.581
    (0.174)
    0.657
    (0.193)
    0.639
    (0.224)
    0.614
    (0.229)
    Lipoprotein(a) Concentration (nmol/L) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [nmol/L]
    31.5
    41.0
    37.0
    33.0
    27.0
    49.0
    53.0
    50.0
    25.0
    61.5
    32.0
    24.5
    34.0
    35.0
    38.0
    32.0
    28.5
    33.0
    41.0
    49.5
    36.5
    28.0
    32.5
    37.0
    34.0
    Triglyceride Concentration (mg/dL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [mg/dL]
    112.0
    108.0
    129.5
    119.0
    135.0
    119.0
    104.0
    104.0
    133.0
    109.0
    104.0
    106.5
    112.5
    134.0
    116.0
    121.0
    128.0
    116.0
    102.0
    119.5
    124.0
    106.0
    129.0
    110.0
    116.0
    Very Low Density Lipoprotein Cholesterol (VLDL-C) Concentration (mg/dL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [mg/dL]
    22.0
    22.0
    25.5
    24.0
    27.0
    24.0
    21.0
    21.0
    26.5
    22.0
    21.0
    21.0
    22.5
    27.0
    23.0
    24.0
    26.0
    23.0
    20.0
    24.0
    25.0
    21.0
    26.0
    22.0
    23.0
    HDL-C Concentration (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    54.1
    (16.6)
    57.9
    (18.4)
    54.1
    (17.2)
    52.7
    (13.7)
    56.0
    (17.9)
    56.1
    (17.8)
    50.6
    (15.6)
    50.9
    (13.0)
    48.7
    (12.6)
    51.6
    (15.1)
    48.5
    (12.9)
    50.8
    (13.5)
    52.1
    (14.9)
    55.5
    (16.0)
    54.5
    (15.0)
    54.0
    (16.0)
    52.8
    (12.9)
    56.0
    (18.7)
    53.2
    (16.4)
    53.8
    (14.6)
    55.0
    (14.2)
    59.9
    (21.8)
    49.7
    (12.6)
    57.3
    (17.4)
    53.5
    (15.9)

    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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    9.86
    (2.53)
    0.97
    (2.82)
    -21.96
    (2.63)
    -17.08
    (2.78)
    -61.56
    (1.81)
    -58.19
    (1.99)
    14.49
    (4.42)
    11.83
    (3.85)
    -14.60
    (4.29)
    -19.80
    (3.85)
    -61.80
    (3.04)
    -58.68
    (2.74)
    8.12
    (2.68)
    5.10
    (2.62)
    -60.09
    (1.94)
    -59.40
    (1.87)
    9.42
    (3.60)
    2.59
    (4.30)
    -58.89
    (2.58)
    -52.40
    (2.98)
    4.70
    (3.61)
    3.40
    (4.94)
    -65.86
    (3.05)
    -57.02
    (3.93)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab Q2W
    Comments The null hypothesis was that there was no 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -71.42
    Confidence Interval (2-Sided) 95%
    -77.55 to -65.29
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.11
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab QM
    Comments The null hypothesis was that there was no 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -59.16
    Confidence Interval (2-Sided) 95%
    -65.94 to -52.38
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.44
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -39.60
    Confidence Interval (2-Sided) 95%
    -45.81 to -33.40
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.15
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -41.10
    Confidence Interval (2-Sided) 95%
    -47.83 to -34.37
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.41
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab Q2W
    Comments The null hypothesis was that there was no 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -76.29
    Confidence Interval (2-Sided) 95%
    -86.87 to -65.72
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.36
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab QM
    Comments The null hypothesis was that there was no 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -70.51
    Confidence Interval (2-Sided) 95%
    -79.81 to -61.20
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.72
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -47.20
    Confidence Interval (2-Sided) 95%
    -57.54 to -36.86
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.24
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -38.88
    Confidence Interval (2-Sided) 95%
    -48.21 to -29.56
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.73
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab Q2W
    Comments The null hypothesis was that there was no 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -68.21
    Confidence Interval (2-Sided) 95%
    -74.72 to -61.70
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.30
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab QM
    Comments The null hypothesis was that there was no 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -64.49
    Confidence Interval (2-Sided) 95%
    -70.84 to -58.14
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.21
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab Q2W
    Comments The null hypothesis was that there was no 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -68.31
    Confidence Interval (2-Sided) 95%
    -77.04 to -59.57
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.42
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab QM
    Comments The null hypothesis was that there was no 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, stratification factors, 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%
    -65.31 to -44.65
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.23
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab Q2W
    Comments The null hypothesis was that there was no 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -70.56
    Confidence Interval (2-Sided) 95%
    -76.72 to -64.41
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.12
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab QM
    Comments The null hypothesis was that there was no 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -60.41
    Confidence Interval (2-Sided) 95%
    -69.11 to -51.72
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.41
    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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    8.54
    (2.24)
    0.35
    (2.60)
    -23.88
    (2.34)
    -18.98
    (2.57)
    -61.41
    (1.61)
    -62.47
    (1.83)
    13.12
    (3.99)
    9.76
    (3.39)
    -16.85
    (3.88)
    -21.25
    (3.42)
    -61.80
    (2.77)
    -65.05
    (2.42)
    7.55
    (2.39)
    2.79
    (2.50)
    -59.33
    (1.74)
    -63.79
    (1.76)
    6.57
    (3.11)
    -0.02
    (3.51)
    -59.08
    (2.23)
    -62.94
    (2.44)
    3.26
    (3.40)
    6.00
    (4.80)
    -66.17
    (2.93)
    -62.45
    (3.85)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab Q2W
    Comments The null hypothesis was that there was no difference in the percent change from Baseline in the average value of LDL-C at Weeks 10 and 12 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -69.95
    Confidence Interval (2-Sided) 95%
    -75.38 to -64.51
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.76
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab QM
    Comments The null hypothesis was that there was no difference in the percent change from Baseline in the average value of LDL-C at Weeks 10 and 12 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -62.82
    Confidence Interval (2-Sided) 95%
    -69.06 to -56.57
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.17
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab Q2W
    Comments The null hypothesis was that there was no difference in the percent change from Baseline in the average value of LDL-C at Weeks 10 and 12 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -37.53
    Confidence Interval (2-Sided) 95%
    -43.03 to -32.03
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.79
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab QM
    Comments The null hypothesis was that there was no difference in the percent change from Baseline in the average value of LDL-C at Weeks 10 and 12 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -43.49
    Confidence Interval (2-Sided) 95%
    -49.70 to -37.28
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.15
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab Q2W
    Comments The null hypothesis was that there was no difference in the percent change from Baseline in the average value of LDL-C at Weeks 10 and 12 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -74.92
    Confidence Interval (2-Sided) 95%
    -84.49 to -65.35
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.85
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab QM
    Comments The null hypothesis was that there was no difference in the percent change from Baseline in the average value of LDL-C at Weeks 10 and 12 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -74.81
    Confidence Interval (2-Sided) 95%
    -83.00 to -66.62
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.15
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab Q2W
    Comments The null hypothesis was that there was no difference in the percent change from Baseline in the average value of LDL-C at Weeks 10 and 12 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -44.95
    Confidence Interval (2-Sided) 95%
    -54.32 to -35.57
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.75
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab QM
    Comments The null hypothesis was that there was no difference in the percent change from Baseline in the average value of LDL-C at Weeks 10 and 12 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -43.81
    Confidence Interval (2-Sided) 95%
    -52.06 to -35.55
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.19
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab Q2W
    Comments The null hypothesis was that there was no difference in the percent change from Baseline in the average value of LDL-C at Weeks 10 and 12 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -66.88
    Confidence Interval (2-Sided) 95%
    -72.67 to -61.08
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.93
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab QM
    Comments The null hypothesis was that there was no difference in the percent change from Baseline in the average value of LDL-C at Weeks 10 and 12 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -66.58
    Confidence Interval (2-Sided) 95%
    -72.60 to -60.56
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.05
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab Q2W
    Comments The null hypothesis was that there was no difference in the percent change from Baseline in the average value of LDL-C at Weeks 10 and 12 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -65.66
    Confidence Interval (2-Sided) 95%
    -73.19 to -58.12
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.81
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab QM
    Comments The null hypothesis was that there was no difference in the percent change from Baseline in the average value of LDL-C at Weeks 10 and 12 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -62.91
    Confidence Interval (2-Sided) 95%
    -71.37 to -54.46
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.27
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab Q2W
    Comments The null hypothesis was that there was no difference in the percent change from Baseline in the average value of LDL-C at Weeks 10 and 12 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -69.43
    Confidence Interval (2-Sided) 95%
    -74.86 to -64.01
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.74
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab QM
    Comments The null hypothesis was that there was no difference in the percent change from Baseline in the average value of LDL-C at Weeks 10 and 12 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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -68.45
    Confidence Interval (2-Sided) 95%
    -76.68 to -60.22
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.17
    Estimation Comments
    3. Secondary Outcome
    Title Change From Baseline in LDL-C at 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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [mg/dL]
    6.8
    (3.7)
    -0.4
    (4.4)
    -32.4
    (3.8)
    -25.1
    (4.3)
    -76.8
    (2.7)
    -80.1
    (3.1)
    11.0
    (5.0)
    5.5
    (3.7)
    -13.0
    (4.9)
    -21.3
    (3.7)
    -58.8
    (3.5)
    -60.1
    (2.6)
    6.5
    (3.5)
    0.1
    (4.2)
    -68.9
    (2.5)
    -77.8
    (3.0)
    3.4
    (3.0)
    -4.8
    (4.2)
    -52.3
    (2.2)
    -55.3
    (2.9)
    -5.7
    (5.2)
    1.7
    (6.5)
    -83.8
    (4.5)
    -78.4
    (5.1)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -83.6
    Confidence Interval (2-Sided) 95%
    -92.6 to -74.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.5
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -79.7
    Confidence Interval (2-Sided) 95%
    -90.2 to -69.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.3
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -44.4
    Confidence Interval (2-Sided) 95%
    -53.4 to -35.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.4
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab 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 included treatment group, stratification factors, 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%
    -65.4 to -44.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.3
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -69.9
    Confidence Interval (2-Sided) 95%
    -81.9 to -57.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.1
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -65.6
    Confidence Interval (2-Sided) 95%
    -74.5 to -56.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.5
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -45.8
    Confidence Interval (2-Sided) 95%
    -57.7 to -33.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.0
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -38.8
    Confidence Interval (2-Sided) 95%
    -47.8 to -29.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.5
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -75.4
    Confidence Interval (2-Sided) 95%
    -83.9 to -67.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.3
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -77.9
    Confidence Interval (2-Sided) 95%
    -88.0 to -67.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.1
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -55.8
    Confidence Interval (2-Sided) 95%
    -63.1 to -48.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.7
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -50.6
    Confidence Interval (2-Sided) 95%
    -60.6 to -40.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.1
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -78.1
    Confidence Interval (2-Sided) 95%
    -86.2 to -70.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.1
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -80.1
    Confidence Interval (2-Sided) 95%
    -91.7 to -68.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.8
    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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [mg/dL]
    8.6
    (4.0)
    0.8
    (4.5)
    -30.1
    (4.1)
    -23.3
    (4.5)
    -77.0
    (2.9)
    -75.1
    (3.2)
    12.7
    (5.3)
    7.0
    (4.1)
    -9.9
    (5.2)
    -19.5
    (4.1)
    -59.0
    (3.7)
    -54.8
    (2.9)
    7.8
    (3.8)
    2.4
    (4.4)
    -69.2
    (2.7)
    -73.3
    (3.1)
    5.1
    (3.2)
    -2.0
    (4.7)
    -52.1
    (2.3)
    -46.7
    (3.3)
    -4.5
    (5.3)
    -0.6
    (6.6)
    -83.5
    (4.6)
    -72.5
    (5.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -85.5
    Confidence Interval (2-Sided) 95%
    -95.2 to -75.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.9
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -75.8
    Confidence Interval (2-Sided) 95%
    -86.8 to -64.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.5
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -46.8
    Confidence Interval (2-Sided) 95%
    -56.6 to -37.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.9
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -51.7
    Confidence Interval (2-Sided) 95%
    -62.6 to -40.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.5
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -71.7
    Confidence Interval (2-Sided) 95%
    -84.4 to -59.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.4
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -61.8
    Confidence Interval (2-Sided) 95%
    -71.6 to -52.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.0
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -49.0
    Confidence Interval (2-Sided) 95%
    -61.5 to -36.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.3
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -35.3
    Confidence Interval (2-Sided) 95%
    -45.2 to -25.5
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.0
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -77.1
    Confidence Interval (2-Sided) 95%
    -86.2 to -67.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.6
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -75.8
    Confidence Interval (2-Sided) 95%
    -86.3 to -65.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.3
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -57.2
    Confidence Interval (2-Sided) 95%
    -65.1 to -49.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.0
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -44.6
    Confidence Interval (2-Sided) 95%
    -55.9 to -33.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.7
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -79.0
    Confidence Interval (2-Sided) 95%
    -87.5 to -70.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.3
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -71.9
    Confidence Interval (2-Sided) 95%
    -83.8 to -60.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.0
    Estimation Comments
    5. 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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    6.80
    (2.07)
    1.28
    (2.44)
    -20.71
    (2.15)
    -16.56
    (2.41)
    -53.48
    (1.48)
    -56.09
    (1.71)
    10.74
    (3.59)
    8.45
    (3.13)
    -16.19
    (3.49)
    -18.79
    (3.16)
    -54.44
    (2.49)
    -56.31
    (2.23)
    7.02
    (2.11)
    3.73
    (2.32)
    -52.59
    (1.54)
    -55.47
    (1.64)
    6.19
    (2.61)
    1.58
    (2.90)
    -52.08
    (1.88)
    -55.72
    (2.01)
    0.74
    (3.23)
    6.81
    (4.35)
    -59.33
    (2.79)
    -56.01
    (3.49)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -60.28
    Confidence Interval (2-Sided) 95%
    -65.29 to -55.27
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.54
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -57.37
    Confidence Interval (2-Sided) 95%
    -63.23 to -51.51
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.97
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -32.77
    Confidence Interval (2-Sided) 95%
    -37.84 to -27.70
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.57
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -39.53
    Confidence Interval (2-Sided) 95%
    -45.34 to -33.71
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.95
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -65.17
    Confidence Interval (2-Sided) 95%
    -73.78 to -56.56
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.37
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -64.76
    Confidence Interval (2-Sided) 95%
    -72.32 to -57.19
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.84
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -38.25
    Confidence Interval (2-Sided) 95%
    -46.68 to -29.81
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.28
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -37.52
    Confidence Interval (2-Sided) 95%
    -45.15 to -29.90
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.87
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -59.61
    Confidence Interval (2-Sided) 95%
    -64.73 to -54.48
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.60
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -59.20
    Confidence Interval (2-Sided) 95%
    -64.80 to -53.60
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.83
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -58.27
    Confidence Interval (2-Sided) 95%
    -64.60 to -51.94
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.20
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -57.31
    Confidence Interval (2-Sided) 95%
    -64.29 to -50.32
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.53
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -60.06
    Confidence Interval (2-Sided) 95%
    -65.18 to -54.94
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.59
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -62.82
    Confidence Interval (2-Sided) 95%
    -70.22 to -55.42
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.75
    Estimation Comments
    6. 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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    8.25
    (2.32)
    2.43
    (2.69)
    -18.27
    (2.40)
    -14.78
    (2.65)
    -53.39
    (1.66)
    -52.20
    (1.90)
    11.79
    (3.87)
    9.95
    (3.51)
    -14.34
    (3.75)
    -17.26
    (3.52)
    -54.84
    (2.66)
    -50.05
    (2.50)
    7.92
    (2.40)
    5.85
    (2.42)
    -52.04
    (1.74)
    -51.57
    (1.72)
    8.61
    (3.04)
    3.35
    (3.53)
    -50.97
    (2.18)
    -46.42
    (2.45)
    1.89
    (3.38)
    5.66
    (4.53)
    -59.02
    (2.87)
    -50.96
    (3.60)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -61.64
    Confidence Interval (2-Sided) 95%
    -67.25 to -56.03
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.84
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -54.93
    Confidence Interval (2-Sided) 95%
    -61.40 to -48.46
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.28
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -35.11
    Confidence Interval (2-Sided) 95%
    -40.79 to -29.44
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.88
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -37.72
    Confidence Interval (2-Sided) 95%
    -44.15 to -31.30
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.26
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -66.64
    Confidence Interval (2-Sided) 95%
    -75.88 to -57.39
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.69
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab 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 included treatment group, stratification factors, 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%
    -68.49 to -51.52
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.30
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -40.51
    Confidence Interval (2-Sided) 95%
    -49.55 to -31.47
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.59
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -32.79
    Confidence Interval (2-Sided) 95%
    -41.30 to -24.28
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.32
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -59.96
    Confidence Interval (2-Sided) 95%
    -65.78 to -54.13
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.95
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -57.42
    Confidence Interval (2-Sided) 95%
    -63.27 to -51.57
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.96
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -59.58
    Confidence Interval (2-Sided) 95%
    -66.95 to -52.21
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.73
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -49.76
    Confidence Interval (2-Sided) 95%
    -58.26 to -41.27
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.30
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -60.91
    Confidence Interval (2-Sided) 95%
    -66.57 to -55.24
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.87
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -56.63
    Confidence Interval (2-Sided) 95%
    -64.63 to -48.62
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.06
    Estimation Comments
    7. 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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    7.55
    (1.89)
    0.81
    (2.19)
    -17.29
    (2.00)
    -11.43
    (2.20)
    -50.95
    (1.38)
    -51.44
    (1.52)
    10.20
    (3.02)
    5.48
    (2.83)
    -14.22
    (2.98)
    -13.62
    (2.87)
    -49.14
    (2.13)
    -53.26
    (2.02)
    5.07
    (1.97)
    2.54
    (1.89)
    -49.79
    (1.46)
    -53.59
    (1.32)
    3.71
    (2.46)
    1.98
    (2.57)
    -47.07
    (1.76)
    -52.95
    (1.76)
    -0.31
    (3.02)
    2.49
    (4.67)
    -55.65
    (2.63)
    -54.37
    (3.93)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -58.49
    Confidence Interval (2-Sided) 95%
    -63.10 to -53.89
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.34
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -52.25
    Confidence Interval (2-Sided) 95%
    -57.49 to -47.01
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.66
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -33.66
    Confidence Interval (2-Sided) 95%
    -38.33 to -28.98
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.37
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -40.01
    Confidence Interval (2-Sided) 95%
    -45.27 to -34.74
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.67
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -59.34
    Confidence Interval (2-Sided) 95%
    -66.61 to -52.07
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.69
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -58.74
    Confidence Interval (2-Sided) 95%
    -65.56 to -51.93
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.46
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -34.92
    Confidence Interval (2-Sided) 95%
    -42.09 to -27.75
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.64
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -39.64
    Confidence Interval (2-Sided) 95%
    -46.57 to -32.71
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.52
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -54.86
    Confidence Interval (2-Sided) 95%
    -59.66 to -50.05
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.43
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -56.14
    Confidence Interval (2-Sided) 95%
    -60.66 to -51.61
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.29
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -50.78
    Confidence Interval (2-Sided) 95%
    -56.72 to -44.83
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.01
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -54.94
    Confidence Interval (2-Sided) 95%
    -61.11 to -48.76
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.12
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -55.34
    Confidence Interval (2-Sided) 95%
    -59.94 to -50.74
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.33
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -56.87
    Confidence Interval (2-Sided) 95%
    -63.27 to -50.46
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.24
    Estimation Comments
    8. 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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    7.89
    (2.16)
    0.21
    (2.43)
    -15.98
    (2.26)
    -10.95
    (2.44)
    -50.90
    (1.56)
    -47.15
    (1.70)
    11.64
    (3.28)
    6.54
    (3.22)
    -12.31
    (3.20)
    -12.16
    (3.24)
    -49.77
    (2.28)
    -46.47
    (2.31)
    6.35
    (2.10)
    4.63
    (2.11)
    -50.15
    (1.54)
    -48.58
    (1.49)
    4.91
    (2.71)
    3.24
    (3.13)
    -45.61
    (1.93)
    -43.71
    (2.13)
    0.35
    (3.17)
    3.57
    (4.74)
    -55.95
    (2.72)
    -49.16
    (3.97)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -58.79
    Confidence Interval (2-Sided) 95%
    -64.03 to -53.55
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.66
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -47.36
    Confidence Interval (2-Sided) 95%
    -53.20 to -41.52
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.96
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -34.92
    Confidence Interval (2-Sided) 95%
    -40.23 to -29.60
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.69
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -36.21
    Confidence Interval (2-Sided) 95%
    -42.06 to -30.35
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.97
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -61.40
    Confidence Interval (2-Sided) 95%
    -69.27 to -53.54
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.99
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -53.01
    Confidence Interval (2-Sided) 95%
    -60.77 to -45.25
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.93
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -37.45
    Confidence Interval (2-Sided) 95%
    -45.17 to -29.74
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.91
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -34.31
    Confidence Interval (2-Sided) 95%
    -42.15 to -26.47
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.98
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, 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%
    -61.60 to -51.40
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.58
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -53.21
    Confidence Interval (2-Sided) 95%
    -58.29 to -48.13
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.57
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -50.52
    Confidence Interval (2-Sided) 95%
    -57.06 to -43.99
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.31
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -46.95
    Confidence Interval (2-Sided) 95%
    -54.43 to -39.47
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.78
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -56.30
    Confidence Interval (2-Sided) 95%
    -61.47 to -51.14
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.61
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -52.73
    Confidence Interval (2-Sided) 95%
    -59.40 to -46.06
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.38
    Estimation Comments
    9. 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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    5.96
    (1.76)
    2.24
    (2.11)
    -14.39
    (1.83)
    -10.86
    (2.08)
    -40.44
    (1.26)
    -42.45
    (1.48)
    4.26
    (2.59)
    6.42
    (2.34)
    -11.92
    (2.52)
    -12.25
    (2.35)
    -40.22
    (1.80)
    -40.43
    (1.66)
    5.41
    (1.96)
    5.02
    (2.25)
    -39.33
    (1.43)
    -42.00
    (1.59)
    4.55
    (1.98)
    1.71
    (2.36)
    -36.04
    (1.42)
    -38.62
    (1.64)
    -0.14
    (2.79)
    5.45
    (3.50)
    -47.20
    (2.37)
    -43.17
    (2.85)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -46.41
    Confidence Interval (2-Sided) 95%
    -50.66 to -42.15
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.16
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -44.69
    Confidence Interval (2-Sided) 95%
    -49.75 to -39.63
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.57
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -26.06
    Confidence Interval (2-Sided) 95%
    -30.36 to -21.75
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.19
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -31.59
    Confidence Interval (2-Sided) 95%
    -36.61 to -26.57
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.55
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -44.48
    Confidence Interval (2-Sided) 95%
    -50.69 to -38.27
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.15
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -46.85
    Confidence Interval (2-Sided) 95%
    -52.48 to -41.21
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.86
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -28.30
    Confidence Interval (2-Sided) 95%
    -34.39 to -22.21
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.09
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -28.18
    Confidence Interval (2-Sided) 95%
    -33.86 to -22.50
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.88
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -44.73
    Confidence Interval (2-Sided) 95%
    -49.50 to -39.97
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.41
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -47.01
    Confidence Interval (2-Sided) 95%
    -52.46 to -41.57
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.75
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -40.59
    Confidence Interval (2-Sided) 95%
    -45.38 to -35.79
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.43
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -40.33
    Confidence Interval (2-Sided) 95%
    -46.00 to -34.66
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.87
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -47.05
    Confidence Interval (2-Sided) 95%
    -51.76 to -42.35
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.38
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -48.62
    Confidence Interval (2-Sided) 95%
    -54.27 to -42.98
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.86
    Estimation Comments
    10. 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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    6.09
    (2.02)
    2.80
    (2.31)
    -12.14
    (2.10)
    -9.85
    (2.28)
    -40.74
    (1.45)
    -40.07
    (1.63)
    4.31
    (2.75)
    6.18
    (2.73)
    -10.53
    (2.66)
    -11.06
    (2.73)
    -40.79
    (1.89)
    -36.25
    (1.94)
    4.68
    (2.28)
    6.07
    (2.36)
    -38.57
    (1.64)
    -39.26
    (1.68)
    5.96
    (2.28)
    2.69
    (2.80)
    -35.17
    (1.63)
    -32.30
    (1.94)
    -0.20
    (2.81)
    5.13
    (3.62)
    -47.24
    (2.38)
    -39.47
    (2.92)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -46.83
    Confidence Interval (2-Sided) 95%
    -51.73 to -41.94
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.48
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -42.86
    Confidence Interval (2-Sided) 95%
    -48.43 to -37.30
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.82
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -28.60
    Confidence Interval (2-Sided) 95%
    -33.56 to -23.65
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.51
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -30.22
    Confidence Interval (2-Sided) 95%
    -35.74 to -24.70
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.80
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -45.10
    Confidence Interval (2-Sided) 95%
    -51.66 to -38.54
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.33
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -42.43
    Confidence Interval (2-Sided) 95%
    -49.01 to -35.85
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.34
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -30.26
    Confidence Interval (2-Sided) 95%
    -36.68 to -23.84
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.26
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -25.19
    Confidence Interval (2-Sided) 95%
    -31.79 to -18.59
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.35
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -43.25
    Confidence Interval (2-Sided) 95%
    -48.77 to -37.74
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.79
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -45.33
    Confidence Interval (2-Sided) 95%
    -51.04 to -39.61
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.89
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -41.13
    Confidence Interval (2-Sided) 95%
    -46.65 to -35.61
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.79
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -34.99
    Confidence Interval (2-Sided) 95%
    -41.72 to -28.25
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.41
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -47.04
    Confidence Interval (2-Sided) 95%
    -51.83 to -42.25
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.43
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -44.60
    Confidence Interval (2-Sided) 95%
    -50.67 to -38.54
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.07
    Estimation Comments
    11. 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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    6.41
    (2.03)
    0.78
    (2.29)
    -15.77
    (2.14)
    -11.47
    (2.29)
    -53.56
    (1.48)
    -53.33
    (1.58)
    4.48
    (3.04)
    5.79
    (2.79)
    -15.17
    (2.99)
    -12.91
    (2.80)
    -52.43
    (2.14)
    -56.20
    (1.98)
    2.82
    (2.26)
    2.58
    (2.05)
    -52.46
    (1.67)
    -56.66
    (1.43)
    2.17
    (2.56)
    2.60
    (2.97)
    -48.47
    (1.83)
    -54.17
    (2.04)
    -1.00
    (3.12)
    -1.42
    (4.22)
    -58.76
    (2.73)
    -57.47
    (3.55)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -59.97
    Confidence Interval (2-Sided) 95%
    -64.91 to -55.03
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.51
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -54.11
    Confidence Interval (2-Sided) 95%
    -59.57 to -48.64
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.77
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -37.79
    Confidence Interval (2-Sided) 95%
    -42.80 to -32.77
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.54
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -41.86
    Confidence Interval (2-Sided) 95%
    -47.34 to -36.67
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.78
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -56.90
    Confidence Interval (2-Sided) 95%
    -64.22 to -49.59
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.71
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -61.99
    Confidence Interval (2-Sided) 95%
    -68.68 to -55.29
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.39
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -37.26
    Confidence Interval (2-Sided) 95%
    -44.48 to -30.04
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.66
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -43.29
    Confidence Interval (2-Sided) 95%
    -50.07 to -36.51
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.44
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -55.29
    Confidence Interval (2-Sided) 95%
    -60.79 to -49.79
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.78
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -59.24
    Confidence Interval (2-Sided) 95%
    -64.16 to -54.32
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.49
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -50.63
    Confidence Interval (2-Sided) 95%
    -56.82 to -44.45
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.13
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -56.78
    Confidence Interval (2-Sided) 95%
    -63.91 to -49.64
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.61
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -57.75
    Confidence Interval (2-Sided) 95%
    -62.51 to -52.99
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.41
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -56.06
    Confidence Interval (2-Sided) 95%
    -61.85 to -50.27
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.93
    Estimation Comments
    12. 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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    6.13
    (2.20)
    -1.21
    (2.41)
    -14.51
    (2.31)
    -12.33
    (2.41)
    -54.17
    (1.59)
    -49.65
    (1.69)
    4.19
    (3.25)
    6.50
    (3.18)
    -13.69
    (3.17)
    -12.19
    (3.17)
    -53.59
    (2.26)
    -50.76
    (2.26)
    1.44
    (2.30)
    4.00
    (2.27)
    -52.97
    (1.69)
    -52.13
    (1.60)
    1.64
    (2.75)
    3.16
    (3.51)
    -47.53
    (1.96)
    -45.65
    (2.39)
    -1.80
    (3.21)
    -0.52
    (4.29)
    -59.53
    (2.77)
    -52.56
    (3.59)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -60.29
    Confidence Interval (2-Sided) 95%
    -65.65 to -54.94
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.71
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -48.44
    Confidence Interval (2-Sided) 95%
    -54.23 to -42.65
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.94
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -39.66
    Confidence Interval (2-Sided) 95%
    -45.09 to -34.23
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.75
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -37.32
    Confidence Interval (2-Sided) 95%
    -43.12 to -31.52
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.94
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -57.77
    Confidence Interval (2-Sided) 95%
    -65.55 to -49.99
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.95
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -57.26
    Confidence Interval (2-Sided) 95%
    -64.91 to -49.60
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.88
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -39.90
    Confidence Interval (2-Sided) 95%
    -47.53 to -32.26
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.87
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -38.57
    Confidence Interval (2-Sided) 95%
    -46.26 to -30.88
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.90
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -54.41
    Confidence Interval (2-Sided) 95%
    -59.99 to -48.82
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.83
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -56.13
    Confidence Interval (2-Sided) 95%
    -61.58 to -50.68
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.76
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -49.17
    Confidence Interval (2-Sided) 95%
    -55.80 to -42.53
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.36
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 included treatment group, stratification factors, 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%
    -57.21 to -40.40
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.25
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -57.73
    Confidence Interval (2-Sided) 95%
    -62.82 to -52.65
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.57
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -52.04
    Confidence Interval (2-Sided) 95%
    -58.10 to -45.98
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.07
    Estimation Comments
    13. 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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Number (95% Confidence Interval) [percentage of participants]
    5.7
    10.2%
    5.6
    10.2%
    20.0
    35.7%
    16.7
    30.4%
    88.1
    80.1%
    85.8
    78%
    13.7
    24.9%
    9.3
    16.9%
    50.9
    90.9%
    62.3
    115.4%
    94.4
    85.8%
    92.5
    84.1%
    7.0
    12.1%
    5.3
    9.3%
    88.7
    77.8%
    89.9
    78.2%
    38.9
    69.5%
    28.8
    51.4%
    93.5
    84.2%
    94.5
    84.4%
    1.9
    3.4%
    3.9
    7.1%
    93.6
    83.6%
    88.5
    77%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage)
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 82.4
    Confidence Interval (2-Sided) 95%
    70.2 to 88.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 80.3
    Confidence Interval (2-Sided) 95%
    67.9 to 86.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 68.1
    Confidence Interval (2-Sided) 95%
    53.1 to 78.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage)
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 69.2
    Confidence Interval (2-Sided) 95%
    54.8 to 78.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 80.7
    Confidence Interval (2-Sided) 95%
    67.3 to 88.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage)
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 83.3
    Confidence Interval (2-Sided) 95%
    70.7 to 89.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 43.5
    Confidence Interval (2-Sided) 95%
    29.5 to 56.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 30.3
    Confidence Interval (2-Sided) 95%
    16.7 to 44.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 81.7
    Confidence Interval (2-Sided) 95%
    69.5 to 88.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 84.6
    Confidence Interval (2-Sided) 95%
    73.1 to 90.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 54.6
    Confidence Interval (2-Sided) 95%
    39.8 to 66.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 65.7
    Confidence Interval (2-Sided) 95%
    51.0 to 76.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 91.7
    Confidence Interval (2-Sided) 95%
    81.6 to 95.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 84.6
    Confidence Interval (2-Sided) 95%
    72.8 to 90.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    14. 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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Number (95% Confidence Interval) [percentage of participants]
    2.0
    3.6%
    5.9
    10.7%
    22.4
    40%
    19.2
    34.9%
    85.4
    77.6%
    84.2
    76.5%
    13.0
    23.6%
    9.8
    17.8%
    52.0
    92.9%
    55.8
    103.3%
    93.1
    84.6%
    91.0
    82.7%
    7.7
    13.3%
    5.5
    9.6%
    85.0
    74.6%
    86.5
    75.2%
    39.6
    70.7%
    28.0
    50%
    92.3
    83.2%
    92.3
    82.4%
    1.9
    3.4%
    6.4
    11.6%
    94.4
    84.3%
    84.8
    73.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage)
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 83.5
    Confidence Interval (2-Sided) 95%
    71.9 to 89.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 78.3
    Confidence Interval (2-Sided) 95%
    65.2 to 85.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 63.0
    Confidence Interval (2-Sided) 95%
    47.3 to 73.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage)
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 64.9
    Confidence Interval (2-Sided) 95%
    49.8 to 75.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 80.1
    Confidence Interval (2-Sided) 95%
    65.8 to 87.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage)
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 81.2
    Confidence Interval (2-Sided) 95%
    67.9 to 88.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 41.1
    Confidence Interval (2-Sided) 95%
    26.4 to 55.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 35.2
    Confidence Interval (2-Sided) 95%
    20.7 to 49.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 77.3
    Confidence Interval (2-Sided) 95%
    63.9 to 84.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 81.1
    Confidence Interval (2-Sided) 95%
    68.8 to 87.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 52.7
    Confidence Interval (2-Sided) 95%
    37.6 to 65.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 64.3
    Confidence Interval (2-Sided) 95%
    49.1 to 75.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 92.5
    Confidence Interval (2-Sided) 95%
    82.3 to 95.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 Cochran-Mantel Haenszel test stratified by the stratification factors (entry statin therapy and simvastatin contraindicated therapy usage).
    Method of Estimation Estimation Parameter Treatment Difference
    Estimated Value 78.4
    Confidence Interval (2-Sided) 95%
    64.9 to 85.4
    Parameter Dispersion Type:
    Value:
    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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    6.07
    (2.86)
    -0.77
    (3.28)
    1.44
    (3.02)
    6.85
    (3.29)
    -26.01
    (2.08)
    -22.64
    (2.27)
    -3.45
    (2.99)
    1.51
    (3.35)
    8.05
    (2.94)
    9.96
    (3.40)
    -23.97
    (2.10)
    -27.46
    (2.39)
    11.41
    (3.00)
    3.65
    (3.56)
    -24.26
    (2.21)
    -23.16
    (2.50)
    8.59
    (2.98)
    6.26
    (3.59)
    -24.96
    (2.12)
    -25.93
    (2.46)
    -10.57
    (4.49)
    -4.99
    (5.37)
    -38.64
    (3.92)
    -32.16
    (4.50)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -32.08
    Confidence Interval (2-Sided) 95%
    -39.06 to -25.11
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.54
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -21.86
    Confidence Interval (2-Sided) 95%
    -29.70 to -14.03
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.98
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -27.45
    Confidence Interval (2-Sided) 95%
    -34.53 to -20.38
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.59
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -29.49
    Confidence Interval (2-Sided) 95%
    -37.36 to -21.62
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.99
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -20.52
    Confidence Interval (2-Sided) 95%
    -27.71 to -13.33
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.65
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -28.96
    Confidence Interval (2-Sided) 95%
    -37.01 to -20.92
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.08
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -32.02
    Confidence Interval (2-Sided) 95%
    -39.11 to -24.93
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.60
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -37.42
    Confidence Interval (2-Sided) 95%
    -45.61 to -29.23
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.15
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -35.66
    Confidence Interval (2-Sided) 95%
    -42.94 to -28.38
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.69
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -26.81
    Confidence Interval (2-Sided) 95%
    -35.36 to -18.27
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.33
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -33.56
    Confidence Interval (2-Sided) 95%
    -40.74 to -26.37
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.64
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -32.19
    Confidence Interval (2-Sided) 95%
    -40.80 to -23.58
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.36
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -28.07
    Confidence Interval (2-Sided) 95%
    -34.91 to -21.23
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.46
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -27.16
    Confidence Interval (2-Sided) 95%
    -34.59 to -19.73
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.76
    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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    7.34
    (3.13)
    -0.43
    (3.38)
    3.29
    (3.28)
    7.18
    (3.38)
    -25.87
    (2.26)
    -20.25
    (2.36)
    -2.23
    (3.35)
    3.41
    (3.54)
    8.01
    (3.26)
    10.20
    (3.57)
    -24.61
    (2.31)
    -24.68
    (2.53)
    11.40
    (3.37)
    4.49
    (3.68)
    -25.09
    (2.47)
    -20.85
    (2.59)
    10.38
    (3.09)
    10.21
    (4.36)
    -26.11
    (2.21)
    -21.97
    (2.97)
    -6.81
    (4.57)
    -1.06
    (5.67)
    -38.06
    (3.96)
    -29.23
    (4.68)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -33.20
    Confidence Interval (2-Sided) 95%
    -40.81 to -25.60
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.86
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -19.82
    Confidence Interval (2-Sided) 95%
    -27.92 to -11.72
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.11
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -29.16
    Confidence Interval (2-Sided) 95%
    -36.87 to -21.44
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.91
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -27.44
    Confidence Interval (2-Sided) 95%
    -35.56 to -19.32
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.12
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -22.38
    Confidence Interval (2-Sided) 95%
    -30.39 to -14.36
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.07
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -28.10
    Confidence Interval (2-Sided) 95%
    -36.62 to -19.58
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.32
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -32.62
    Confidence Interval (2-Sided) 95%
    -40.46 to -24.78
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.98
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -34.88
    Confidence Interval (2-Sided) 95%
    -43.52 to -26.25
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.38
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -36.50
    Confidence Interval (2-Sided) 95%
    -44.69 to -28.30
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.15
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -25.34
    Confidence Interval (2-Sided) 95%
    -34.19 to -16.49
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.48
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -36.48
    Confidence Interval (2-Sided) 95%
    -43.95 to -29.02
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.78
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -32.17
    Confidence Interval (2-Sided) 95%
    -42.61 to -21.74
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.28
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -31.25
    Confidence Interval (2-Sided) 95%
    -38.40 to -24.10
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.62
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -28.17
    Confidence Interval (2-Sided) 95%
    -36.79 to -19.55
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.36
    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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    6.49
    (3.94)
    9.17
    (4.41)
    -3.16
    (4.10)
    1.57
    (4.35)
    -5.61
    (2.81)
    -13.38
    (3.08)
    6.16
    (4.02)
    8.05
    (4.35)
    -8.10
    (3.92)
    -4.86
    (4.39)
    -9.27
    (2.80)
    -6.36
    (3.11)
    12.43
    (4.19)
    12.26
    (4.67)
    -10.28
    (3.04)
    -7.26
    (3.29)
    8.44
    (3.76)
    10.75
    (3.98)
    -9.15
    (2.70)
    -15.43
    (2.77)
    9.29
    (6.97)
    13.78
    (7.44)
    -11.67
    (5.97)
    -15.93
    (6.15)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.20
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -12.10
    Confidence Interval (2-Sided) 95%
    -21.63 to -2.58
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.83
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -22.55
    Confidence Interval (2-Sided) 95%
    -33.13 to -11.97
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.36
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 1.00
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -2.45
    Confidence Interval (2-Sided) 95%
    -12.09 to 7.19
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.89
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.053
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -14.95
    Confidence Interval (2-Sided) 95%
    -25.46 to -4.44
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.33
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.073
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -15.43
    Confidence Interval (2-Sided) 95%
    -25.06 to -5.79
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.89
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab QM
    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 Repeated measures linear effects model
    Comments The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -14.41
    Confidence Interval (2-Sided) 95%
    -24.90 to -3.92
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.32
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 1.00
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -1.17
    Confidence Interval (2-Sided) 95%
    -10.63 to 8.30
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.80
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.63
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -1.51
    Confidence Interval (2-Sided) 95%
    -12.12 to 9.11
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.38
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -22.72
    Confidence Interval (2-Sided) 95%
    -32.90 to -12.54
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.15
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab QM
    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 Repeated measures linear effects model
    Comments The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -19.52
    Confidence Interval (2-Sided) 95%
    -30.76 to -8.28
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.69
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -17.59
    Confidence Interval (2-Sided) 95%
    -26.71 to -8.46
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.62
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -26.18
    Confidence Interval (2-Sided) 95%
    -35.76 to -16.59
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.85
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, 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%
    -32.38 to -9.55
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.78
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -29.71
    Confidence Interval (2-Sided) 95%
    -40.84 to -18.57
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.64
    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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    8.27
    (5.23)
    14.35
    (5.92)
    -0.43
    (5.39)
    4.88
    (5.84)
    -3.79
    (3.72)
    -13.26
    (4.17)
    6.65
    (4.45)
    8.22
    (5.22)
    -7.40
    (4.32)
    -3.11
    (5.23)
    -10.07
    (3.05)
    -1.10
    (3.74)
    13.57
    (5.76)
    12.96
    (5.32)
    -4.46
    (4.16)
    -6.88
    (3.80)
    10.97
    (4.66)
    10.00
    (4.38)
    -5.58
    (3.34)
    -10.51
    (3.04)
    8.07
    (6.88)
    16.72
    (7.88)
    -13.71
    (5.91)
    -14.65
    (6.39)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.20
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -12.06
    Confidence Interval (2-Sided) 95%
    -24.69 to 0.57
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.41
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -27.60
    Confidence Interval (2-Sided) 95%
    -41.86 to -13.35
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.23
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 1.00
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -3.37
    Confidence Interval (2-Sided) 95%
    -16.16 to 9.43
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.49
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.053
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -18.13
    Confidence Interval (2-Sided) 95%
    -32.28 to -3.99
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.18
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.073
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -16.72
    Confidence Interval (2-Sided) 95%
    -27.34 to -6.10
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.39
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab QM
    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 Repeated measures linear effects model
    Comments The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -9.31
    Confidence Interval (2-Sided) 95%
    -21.92 to 3.29
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.39
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 1.00
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -2.67
    Confidence Interval (2-Sided) 95%
    -13.05 to 7.72
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.27
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.63
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 2.02
    Confidence Interval (2-Sided) 95%
    -10.66 to 14.69
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.43
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -18.03
    Confidence Interval (2-Sided) 95%
    -32.03 to -4.04
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.08
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab QM
    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 Repeated measures linear effects model
    Comments The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -19.83
    Confidence Interval (2-Sided) 95%
    -32.71 to -6.96
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.52
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -16.55
    Confidence Interval (2-Sided) 95%
    -27.84 to -5.26
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.71
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -20.51
    Confidence Interval (2-Sided) 95%
    -31.04 to -9.98
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.33
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -21.78
    Confidence Interval (2-Sided) 95%
    -32.88 to -10.68
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.62
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -31.36
    Confidence Interval (2-Sided) 95%
    -44.10 to -18.62
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.45
    Estimation Comments
    19. Secondary Outcome
    Title Percent Change From Baseline in Very Low-Density 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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    6.51
    (3.56)
    9.53
    (4.45)
    -5.35
    (3.74)
    1.77
    (4.41)
    -6.85
    (2.56)
    -11.77
    (3.11)
    6.24
    (4.03)
    8.31
    (4.26)
    -8.52
    (3.93)
    -6.13
    (4.31)
    -8.96
    (2.82)
    -6.38
    (3.05)
    12.86
    (3.95)
    12.54
    (4.58)
    -12.22
    (2.86)
    -7.25
    (3.23)
    7.06
    (3.76)
    8.13
    (3.72)
    -9.09
    (2.71)
    -15.05
    (2.58)
    8.64
    (6.01)
    16.37
    (7.15)
    -14.57
    (5.17)
    -16.50
    (5.87)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.088
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -13.36
    Confidence Interval (2-Sided) 95%
    -21.99 to -4.74
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.38
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -21.31
    Confidence Interval (2-Sided) 95%
    -31.98 to -10.64
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.41
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 1.00
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -1.50
    Confidence Interval (2-Sided) 95%
    -10.27 to 7.27
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.45
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.056
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -13.54
    Confidence Interval (2-Sided) 95%
    -24.17 to -2.91
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.39
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.073
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -15.21
    Confidence Interval (2-Sided) 95%
    -24.88 to -5.54
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.91
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab QM
    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 Repeated measures linear effects model
    Comments The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -14.69
    Confidence Interval (2-Sided) 95%
    -24.97 to -4.42
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.21
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 1.00
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -0.44
    Confidence Interval (2-Sided) 95%
    -9.94 to 9.05
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.82
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.62
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -0.25
    Confidence Interval (2-Sided) 95%
    -10.66 to 10.16
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.28
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -25.07
    Confidence Interval (2-Sided) 95%
    -34.64 to -15.50
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.85
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab QM
    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 Repeated measures linear effects model
    Comments The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -19.79
    Confidence Interval (2-Sided) 95%
    -30.81 to -8.77
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.58
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -16.15
    Confidence Interval (2-Sided) 95%
    -25.27 to -7.03
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.61
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -23.18
    Confidence Interval (2-Sided) 95%
    -32.11 to -14.25
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.52
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -23.21
    Confidence Interval (2-Sided) 95%
    -33.00 to -13.43
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.95
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -32.87
    Confidence Interval (2-Sided) 95%
    -43.60 to -22.14
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.43
    Estimation Comments
    20. Secondary Outcome
    Title Percent Change From Baseline in Very Low-Density Cholesterol (VLDL-C) at Week 12
    Description
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set
    Arm/Group Title A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    8.32
    (4.00)
    14.74
    (5.91)
    -4.61
    (4.19)
    3.45
    (5.89)
    -6.16
    (2.88)
    -11.73
    (4.16)
    6.73
    (4.45)
    8.54
    (5.00)
    -7.92
    (4.32)
    -6.00
    (5.04)
    -9.69
    (3.05)
    -1.06
    (3.58)
    13.79
    (5.05)
    12.47
    (5.31)
    -8.20
    (3.64)
    -6.28
    (3.78)
    10.09
    (4.65)
    8.59
    (4.37)
    -6.10
    (3.33)
    -9.95
    (3.03)
    7.63
    (6.26)
    20.97
    (7.53)
    -14.83
    (5.30)
    -15.86
    (6.09)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.088
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -14.47
    Confidence Interval (2-Sided) 95%
    -24.16 to -4.78
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.92
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -26.47
    Confidence Interval (2-Sided) 95%
    -40.71 to -12.24
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.22
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 1.00
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -1.54
    Confidence Interval (2-Sided) 95%
    -11.41 to 8.32
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.00
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.056
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -15.19
    Confidence Interval (2-Sided) 95%
    -29.40 to -0.97
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 7.21
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.073
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -16.42
    Confidence Interval (2-Sided) 95%
    -27.05 to -5.80
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.39
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab QM
    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 Repeated measures linear effects model
    Comments The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -9.60
    Confidence Interval (2-Sided) 95%
    -21.68 to 2.48
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.13
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 1.00
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -1.78
    Confidence Interval (2-Sided) 95%
    -12.16 to 8.61
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.27
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.62
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 4.94
    Confidence Interval (2-Sided) 95%
    -7.25 to 17.14
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.18
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -21.98
    Confidence Interval (2-Sided) 95%
    -34.24 to -9.73
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.20
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab QM
    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 Repeated measures linear effects model
    Comments The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -18.75
    Confidence Interval (2-Sided) 95%
    -31.60 to -5.90
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.50
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.005
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -16.19
    Confidence Interval (2-Sided) 95%
    -27.46 to -4.92
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.70
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -18.54
    Confidence Interval (2-Sided) 95%
    -29.04 to -8.05
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.31
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -22.45
    Confidence Interval (2-Sided) 95%
    -33.09 to -11.81
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.39
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -36.83
    Confidence Interval (2-Sided) 95%
    -48.96 to -24.70
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 6.14
    Estimation Comments
    21. 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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    -0.99
    (1.50)
    -0.45
    (1.94)
    -1.13
    (1.56)
    -0.92
    (1.92)
    5.54
    (1.07)
    7.66
    (1.37)
    4.48
    (1.73)
    -1.37
    (1.85)
    0.86
    (1.68)
    -0.59
    (1.86)
    8.44
    (1.20)
    7.76
    (1.31)
    0.87
    (1.52)
    -0.94
    (2.55)
    6.23
    (1.10)
    7.72
    (1.80)
    -0.60
    (1.56)
    -0.40
    (1.81)
    4.86
    (1.12)
    6.35
    (1.26)
    0.13
    (2.75)
    -2.14
    (2.72)
    10.35
    (2.26)
    6.71
    (2.25)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.034
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 6.53
    Confidence Interval (2-Sided) 95%
    2.91 to 10.15
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.84
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 8.11
    Confidence Interval (2-Sided) 95%
    3.43 to 12.79
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.37
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 6.67
    Confidence Interval (2-Sided) 95%
    3.00 to 10.34
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.86
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 8.57
    Confidence Interval (2-Sided) 95%
    3.93 to 13.22
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.36
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.85
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 3.95
    Confidence Interval (2-Sided) 95%
    -0.19 to 8.09
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.10
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 9.13
    Confidence Interval (2-Sided) 95%
    4.68 to 13.58
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.26
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 7.57
    Confidence Interval (2-Sided) 95%
    3.51 to 11.64
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.06
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 8.35
    Confidence Interval (2-Sided) 95%
    3.86 to 12.84
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.28
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 5.36
    Confidence Interval (2-Sided) 95%
    1.68 to 9.04
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.87
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.010
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 8.66
    Confidence Interval (2-Sided) 95%
    2.51 to 14.80
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.11
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab 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 Repeated measures linear effects model
    Comments The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 5.46
    Confidence Interval (2-Sided) 95%
    1.69 to 9.23
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.91
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 6.75
    Confidence Interval (2-Sided) 95%
    2.40 to 11.10
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.20
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 10.23
    Confidence Interval (2-Sided) 95%
    5.13 to 15.32
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.58
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 8.85
    Confidence Interval (2-Sided) 95%
    4.73 to 12.97
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.09
    Estimation Comments
    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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    Measure Participants 56 55 56 55 110 110 55 55 56 54 109 110 58 57 113 115 56 55 111 112 56 55 112 115
    Least Squares Mean (Standard Error) [percent change]
    0.22
    (1.72)
    0.01
    (2.02)
    -1.76
    (1.78)
    -0.40
    (1.99)
    7.04
    (1.23)
    7.88
    (1.42)
    5.02
    (1.88)
    0.30
    (2.01)
    0.62
    (1.83)
    0.21
    (2.01)
    9.09
    (1.29)
    7.36
    (1.43)
    2.87
    (1.87)
    -0.16
    (2.64)
    6.07
    (1.35)
    7.18
    (1.87)
    -0.39
    (1.86)
    0.73
    (1.98)
    4.65
    (1.34)
    5.57
    (1.37)
    1.14
    (2.96)
    -2.65
    (2.87)
    10.92
    (2.38)
    6.41
    (2.34)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection A10 PBO Q2W, A10 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.034
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 6.83
    Confidence Interval (2-Sided) 95%
    2.66 to 10.99
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.11
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection A10 PBO QM, A10 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.017
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 7.87
    Confidence Interval (2-Sided) 95%
    3.01 to 12.73
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.46
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection A10 EZE (Q2W), A10 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 8.81
    Confidence Interval (2-Sided) 95%
    4.58 to 13.03
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.14
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection A10 EZE (QM), A10 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 8.28
    Confidence Interval (2-Sided) 95%
    3.46 to 13.11
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.45
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection A80 PBO Q2W, A80 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.85
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 4.07
    Confidence Interval (2-Sided) 95%
    -0.42 to 8.57
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.28
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection A80 PBO QM, A80 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 7.05
    Confidence Interval (2-Sided) 95%
    2.22 to 11.89
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.45
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection A80 EZE (Q2W), A80 EvoMab Q2W
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 8.47
    Confidence Interval (2-Sided) 95%
    4.07 to 12.87
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.23
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection A80 EZE (QM), A80 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 7.14
    Confidence Interval (2-Sided) 95%
    2.29 to 11.99
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.46
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection R5 PBO Q2W, R5 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 3.20
    Confidence Interval (2-Sided) 95%
    -1.33 to 7.73
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.30
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection R5 PBO QM, R5 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.010
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 7.35
    Confidence Interval (2-Sided) 95%
    0.97 to 13.72
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.23
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection R40 PBO Q2W, R40 EvoMab 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 Repeated measures linear effects model
    Comments The model included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 5.04
    Confidence Interval (2-Sided) 95%
    0.52 to 9.56
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.29
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection R40 PBO QM, R40 EvoMab QM
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.002
    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, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 4.84
    Confidence Interval (2-Sided) 95%
    0.07 to 9.60
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.41
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection S40 PBO Q2W, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 9.78
    Confidence Interval (2-Sided) 95%
    4.05 to 15.51
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.90
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection S40 PBO QM, S40 EvoMab 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 included treatment group, stratification factors, scheduled visit and the interaction of treatment with scheduled visit
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value 9.06
    Confidence Interval (2-Sided) 95%
    4.40 to 13.72
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.36
    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 A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab QM
    Arm/Group Description Participants received atorvastatin 10 mg once daily during the 4 week lipid stabilization period and then in combination with placebo (PBO) subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month (QM) and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe (EZE) orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab (EvoMab) by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 10 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month and 10 mg ezetimibe orally once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once daily for up to 12 weeks. Participants received atorvastatin 80 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once daily for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received rosuvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once a month for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. Participants received simvastatin 40 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks.
    All Cause Mortality
    A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab 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 Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events 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) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab 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 Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events 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 1/56 (1.8%) 2/55 (3.6%) 0/56 (0%) 0/55 (0%) 4/110 (3.6%) 2/110 (1.8%) 2/55 (3.6%) 1/55 (1.8%) 1/56 (1.8%) 1/54 (1.9%) 3/109 (2.8%) 1/110 (0.9%) 1/58 (1.7%) 2/57 (3.5%) 3/113 (2.7%) 3/115 (2.6%) 2/56 (3.6%) 1/55 (1.8%) 1/111 (0.9%) 3/112 (2.7%) 0/56 (0%) 1/55 (1.8%) 2/112 (1.8%) 1/115 (0.9%)
    Cardiac disorders
    Acute coronary syndrome 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 1/110 (0.9%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Acute myocardial infarction 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 1/110 (0.9%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 1/115 (0.9%) 1/56 (1.8%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Myocardial infarction 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 1/109 (0.9%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Ventricular fibrillation 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 1/109 (0.9%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Gastrointestinal disorders
    Abdominal pain upper 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 1/113 (0.9%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Gastrointestinal haemorrhage 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 1/55 (1.8%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 1/55 (1.8%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Hiatus hernia 1/56 (1.8%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Hepatobiliary disorders
    Cholecystitis 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 1/112 (0.9%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Drug-induced liver injury 0/56 (0%) 1/55 (1.8%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Infections and infestations
    Campylobacter infection 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 1/113 (0.9%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Gastroenteritis 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 1/55 (1.8%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Herpes simplex meningoencephalitis 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 1/55 (1.8%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Infected bites 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 1/109 (0.9%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Pneumonia 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 1/110 (0.9%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Pneumonia mycoplasmal 0/56 (0%) 1/55 (1.8%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Pyelonephritis acute 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 1/110 (0.9%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Urinary tract infection bacterial 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 1/57 (1.8%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Injury, poisoning and procedural complications
    Injury 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 1/112 (0.9%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Radius fracture 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 1/115 (0.9%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Investigations
    Troponin increased 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 1/54 (1.9%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 1/111 (0.9%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Musculoskeletal and connective tissue disorders
    Myalgia 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 1/55 (1.8%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Rotator cuff syndrome 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 1/110 (0.9%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Spinal pain 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 1/115 (0.9%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Bladder neoplasm 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 1/56 (1.8%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Colon cancer metastatic 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 1/112 (0.9%) 0/115 (0%)
    Lung adenocarcinoma metastatic 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 1/113 (0.9%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Ovarian cancer 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 1/57 (1.8%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Pleomorphic adenoma 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 1/58 (1.7%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Nervous system disorders
    Cerebrovascular accident 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 1/56 (1.8%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Coma 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 1/109 (0.9%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Grand mal convulsion 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 1/55 (1.8%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Ischaemic stroke 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 1/112 (0.9%) 0/115 (0%)
    Psychiatric disorders
    Affective disorder 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 1/110 (0.9%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Renal and urinary disorders
    Glomerulonephritis acute 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 1/112 (0.9%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Renal failure acute 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 1/115 (0.9%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Reproductive system and breast disorders
    Breast pain 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 1/110 (0.9%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary oedema 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 1/109 (0.9%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Surgical and medical procedures
    Hip arthroplasty 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 1/110 (0.9%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Vascular disorders
    Aortic aneurysm 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 1/109 (0.9%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Hypertensive crisis 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 1/54 (1.9%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Orthostatic hypotension 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 1/111 (0.9%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 0/112 (0%) 0/115 (0%)
    Peripheral artery stenosis 0/56 (0%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 0/55 (0%) 0/55 (0%) 0/56 (0%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 0/113 (0%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 1/55 (1.8%) 0/112 (0%) 0/115 (0%)
    Other (Not Including Serious) Adverse Events
    A10 PBO Q2W A10 PBO QM A10 EZE (Q2W) A10 EZE (QM) A10 EvoMab Q2W A10 EvoMab QM A80 PBO Q2W A80 PBO QM A80 EZE (Q2W) A80 EZE (QM) A80 EvoMab Q2W A80 EvoMab QM R5 PBO Q2W R5 PBO QM R5 EvoMab Q2W R5 EvoMab QM R40 PBO Q2W R40 PBO QM R40 EvoMab Q2W R40 EvoMab QM S40 PBO Q2W S40 PBO QM S40 EvoMab Q2W S40 EvoMab 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 Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events 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 5/56 (8.9%) 3/55 (5.5%) 9/56 (16.1%) 6/55 (10.9%) 9/110 (8.2%) 7/110 (6.4%) 7/55 (12.7%) 13/55 (23.6%) 8/56 (14.3%) 2/54 (3.7%) 11/109 (10.1%) 9/110 (8.2%) 11/58 (19%) 1/57 (1.8%) 6/113 (5.3%) 9/115 (7.8%) 3/56 (5.4%) 8/55 (14.5%) 5/111 (4.5%) 8/112 (7.1%) 3/56 (5.4%) 5/55 (9.1%) 18/112 (16.1%) 11/115 (9.6%)
    Gastrointestinal disorders
    Constipation 3/56 (5.4%) 0/55 (0%) 0/56 (0%) 0/55 (0%) 0/110 (0%) 0/110 (0%) 1/55 (1.8%) 0/55 (0%) 1/56 (1.8%) 0/54 (0%) 0/109 (0%) 0/110 (0%) 0/58 (0%) 0/57 (0%) 1/113 (0.9%) 0/115 (0%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 0/112 (0%) 0/56 (0%) 0/55 (0%) 2/112 (1.8%) 0/115 (0%)
    Diarrhoea 0/56 (0%) 0/55 (0%) 0/56 (0%) 1/55 (1.8%) 2/110 (1.8%) 0/110 (0%) 1/55 (1.8%) 4/55 (7.3%) 1/56 (1.8%) 0/54 (0%) 4/109 (3.7%) 2/110 (1.8%) 0/58 (0%) 1/57 (1.8%) 0/113 (0%) 2/115 (1.7%) 1/56 (1.8%) 1/55 (1.8%) 0/111 (0%) 1/112 (0.9%) 0/56 (0%) 1/55 (1.8%) 1/112 (0.9%) 0/115 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/56 (0%) 0/55 (0%) 3/56 (5.4%) 1/55 (1.8%) 2/110 (1.8%) 1/110 (0.9%) 2/55 (3.6%) 2/55 (3.6%) 2/56 (3.6%) 1/54 (1.9%) 3/109 (2.8%) 0/110 (0%) 4/58 (6.9%) 0/57 (0%) 1/113 (0.9%) 2/115 (1.7%) 0/56 (0%) 5/55 (9.1%) 2/111 (1.8%) 1/112 (0.9%) 0/56 (0%) 1/55 (1.8%) 6/112 (5.4%) 2/115 (1.7%)
    Muscle spasms 0/56 (0%) 0/55 (0%) 1/56 (1.8%) 2/55 (3.6%) 3/110 (2.7%) 4/110 (3.6%) 1/55 (1.8%) 2/55 (3.6%) 3/56 (5.4%) 0/54 (0%) 2/109 (1.8%) 1/110 (0.9%) 1/58 (1.7%) 0/57 (0%) 2/113 (1.8%) 0/115 (0%) 0/56 (0%) 1/55 (1.8%) 0/111 (0%) 1/112 (0.9%) 0/56 (0%) 1/55 (1.8%) 3/112 (2.7%) 1/115 (0.9%)
    Myalgia 2/56 (3.6%) 2/55 (3.6%) 2/56 (3.6%) 0/55 (0%) 0/110 (0%) 1/110 (0.9%) 0/55 (0%) 3/55 (5.5%) 1/56 (1.8%) 1/54 (1.9%) 1/109 (0.9%) 2/110 (1.8%) 1/58 (1.7%) 0/57 (0%) 0/113 (0%) 2/115 (1.7%) 0/56 (0%) 1/55 (1.8%) 1/111 (0.9%) 1/112 (0.9%) 0/56 (0%) 1/55 (1.8%) 1/112 (0.9%) 3/115 (2.6%)
    Nervous system disorders
    Dizziness 0/56 (0%) 0/55 (0%) 2/56 (3.6%) 1/55 (1.8%) 1/110 (0.9%) 1/110 (0.9%) 1/55 (1.8%) 1/55 (1.8%) 1/56 (1.8%) 1/54 (1.9%) 0/109 (0%) 1/110 (0.9%) 3/58 (5.2%) 0/57 (0%) 1/113 (0.9%) 2/115 (1.7%) 0/56 (0%) 0/55 (0%) 0/111 (0%) 1/112 (0.9%) 1/56 (1.8%) 0/55 (0%) 3/112 (2.7%) 1/115 (0.9%)
    Headache 1/56 (1.8%) 1/55 (1.8%) 1/56 (1.8%) 4/55 (7.3%) 1/110 (0.9%) 0/110 (0%) 2/55 (3.6%) 2/55 (3.6%) 0/56 (0%) 0/54 (0%) 1/109 (0.9%) 3/110 (2.7%) 3/58 (5.2%) 0/57 (0%) 1/113 (0.9%) 1/115 (0.9%) 2/56 (3.6%) 1/55 (1.8%) 2/111 (1.8%) 3/112 (2.7%) 2/56 (3.6%) 1/55 (1.8%) 2/112 (1.8%) 5/115 (4.3%)

    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:
    NCT01763866
    Other Study ID Numbers:
    • 20110115
    • 2012-001363-70
    First Posted:
    Jan 9, 2013
    Last Update Posted:
    Jan 14, 2021
    Last Verified:
    Jul 1, 2020