Monoclonal Antibody Against PCSK9 to Reduce Elevated Low-... | NCT01375777 | Trialant
NCT01375777
Sponsor
Amgen
Status
Completed
Last Update Posted
Nov 8, 2022Actual
Enrollment
411Actual
Phase
Phase 2
Conditions
Hyperlipidemia
Interventions
Evolocumab
Ezetimibe
Placebo to Evolocumab
Countries
United States
Australia
Belgium
Canada
Denmark
Protocol Section
Identification Module
NCT ID
NCT01375777
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
20101154
Secondary IDs
Not provided
Brief Title
Monoclonal Antibody Against PCSK9 to Reduce Elevated Low-density Lipoprotein Cholesterol (LDL-C) in Adults Currently Not Receiving Drug Therapy for Easing Lipid Levels
Official Title
A Randomized, Placebo- and Ezetimibe-controlled, Dose-ranging Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Hypercholesterolemic Subjects With a 10-year Framingham Risk Score of 10% or Less
Acronym
MENDEL
Organization
AmgenINDUSTRY
Status Module
Record Verification Date
Nov 2022
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jul 6, 2011Actual
Primary Completion Date
Mar 2, 2012Actual
Completion Date
Mar 2, 2012Actual
First Submitted Date
Jun 16, 2011
First Submission Date that Met QC Criteria
Jun 16, 2011
First Posted Date
Jun 17, 2011Estimated
Results Waived
Not provided
Results First Submitted Date
Sep 3, 2015
Results First Submitted that Met QC Criteria
Sep 3, 2015
Results First Posted Date
Oct 5, 2015Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Mar 26, 2013
Certification/Extension First Submitted that Passed QC Review
Apr 2, 2013
Certification/Extension First Posted Date
Apr 9, 2013Estimated
Last Update Submitted Date
Nov 4, 2022
Last Update Posted Date
Nov 8, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
AmgenINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The primary objective was to evaluate the effect of 12 weeks of subcutaneous evolocumab (AMG 145) every 2 weeks (Q2W) or every 4 weeks (Q4W), compared with placebo, on the percent change from baseline in LDL-C when used as monotherapy in adults with hypercholesterolemia.
Detailed Description
Not provided
Conditions Module
Conditions
Hyperlipidemia
Keywords
High cholesterol
Proprotein convertase subtilisin/kexin type 9 (PCSK9)
Treatment for high cholesterol
Lowering cholesterol
Lowering high cholesterol
Hypercholesterolemia
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
411Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Placebo Q2W
Placebo Comparator
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
Other: Placebo to Evolocumab
Placebo Q4W
Placebo Comparator
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
Other: Placebo to Evolocumab
Ezetimibe
Active Comparator
Participants received 10 mg ezetimibe orally once a day for 12 weeks.
Drug: Ezetimibe
Evolocumab 70 mg Q2W
Experimental
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Biological: Evolocumab
Evolocumab 105 mg Q2W
Experimental
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Biological: Evolocumab
Evolocumab 140 mg Q2W
Experimental
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Evolocumab
Biological
Administered by subcutaneous injection
Evolocumab 105 mg Q2W
Evolocumab 140 mg Q2W
Evolocumab 280 mg Q4W
Evolocumab 350 mg Q4W
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
LDL-C was measured using ultracentrifugation.
Baseline and Week 12
Secondary Outcomes
Measure
Description
Time Frame
Change From Baseline in LDL-C at Week 12
LDL-C was measured using ultracentrifugation.
Baseline and Week 12
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Male or female ≥ 18 to ≤ 75 years of age
Low density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL and < 190 mg/dL
Framingham risk score of 10% or less
Fasting triglycerides < 400 mg/dL
Exclusion Criteria:
History of coronary heart disease
New York Heart Association (NYHA) II - IV heart failure
Koren MJ, Scott R, Kim JB, Knusel B, Liu T, Lei L, Bolognese M, Wasserman SM. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet. 2012 Dec 8;380(9858):1995-2006. doi: 10.1016/S0140-6736(12)61771-1. Epub 2012 Nov 6.
Participants were randomized with equal allocation into 1 of 9 treatment groups. Randomization was stratified on the basis of screening LDL-C concentration (< 130 mg/dL [3.4 mmol/L] or ≥ 130 mg/dL).
Recruitment Details
This study enrolled adults 18 - 75 years with fasting low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL and < 190 mg/dL, fasting triglycerides ≤ 400 mg/dL and a National Cholesterol Education Program Adult Treatment Panel III Framingham risk score of 10% or less. First patient enrolled 06 July 2011, last patient enrolled 25 November 2011.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Placebo Q2W
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
FG001
Placebo Q4W
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
LDL-C was measured using ultracentrifugation.
Full analysis set; missing ultracentrifugation (UC) LDL-C at Week 12 was imputed using last observation carried forward (LOCF) and calculated LDL-C.
Posted
Least Squares Mean
Standard Error
percent change
Baseline and Week 12
ID
Title
Description
OG000
Placebo Q2W
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
OG001
Placebo Q4W
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
OG002
Ezetimibe
Participants received 10 mg ezetimibe orally once a day for 12 weeks.
OG003
Evolocumab 70 mg Q2W
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG004
Evolocumab 105 mg Q2W
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG005
Evolocumab 140 mg Q2W
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG006
Evolocumab 280 mg Q4W
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG007
Evolocumab 350 mg Q4W
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG008
Evolocumab 420 mg Q4W
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Units
Counts
Participants
OG00045
OG00145
OG00245
OG003
Title
Denominators
Categories
Title
Measurements
OG000-3.71± 2.66
OG0014.54± 2.64
OG002-14.26± 2.60
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG005
The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
LS Mean Treatment Difference
-47.23
Standard Error of the Mean
3.70
2-Sided
95
-54.52
-39.93
Placebo is the reference
Secondary
Change From Baseline in LDL-C at Week 12
LDL-C was measured using ultracentrifugation.
Full analysis set; missing ultracentrifugation (UC) LDL-C at Week 12 was imputed using LOCF.
Posted
Least Squares Mean
Standard Error
mg/dL
Baseline and Week 12
ID
Title
Description
OG000
Placebo Q2W
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
OG001
Placebo Q4W
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
OG002
Ezetimibe
Participants received 10 mg ezetimibe orally once a day for 12 weeks.
OG003
Evolocumab 70 mg Q2W
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG004
Evolocumab 105 mg Q2W
Secondary
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12
Full analysis set; missing data at Week 12 were imputed using LOCF.
Posted
Least Squares Mean
Standard Error
percent change
Baseline and Week 12
ID
Title
Description
OG000
Placebo Q2W
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
OG001
Placebo Q4W
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
OG002
Ezetimibe
Participants received 10 mg ezetimibe orally once a day for 12 weeks.
OG003
Evolocumab 70 mg Q2W
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG004
Evolocumab 105 mg Q2W
Secondary
Percent Change From Baseline in Apolipoprotein B at Week 12
Full analysis set; missing data at Week 12 were imputed using LOCF.
Posted
Least Squares Mean
Standard Error
percent change
Baseline and Week 12
ID
Title
Description
OG000
Placebo Q2W
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
OG001
Placebo Q4W
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
OG002
Ezetimibe
Participants received 10 mg ezetimibe orally once a day for 12 weeks.
OG003
Evolocumab 70 mg Q2W
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG004
Evolocumab 105 mg Q2W
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Secondary
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12
Full analysis set; missing data at Week 12 were imputed using LOCF.
Posted
Least Squares Mean
Standard Error
percent change
Baseline and Week 12
ID
Title
Description
OG000
Placebo Q2W
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
OG001
Placebo Q4W
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
OG002
Ezetimibe
Participants received 10 mg ezetimibe orally once a day for 12 weeks.
OG003
Evolocumab 70 mg Q2W
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG004
Evolocumab 105 mg Q2W
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Secondary
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12
Full analysis set; missing data at Week 12 were imputed using LOCF.
Posted
Least Squares Mean
Standard Error
percent change
Baseline and Week 12
ID
Title
Description
OG000
Placebo Q2W
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
OG001
Placebo Q4W
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
OG002
Ezetimibe
Participants received 10 mg ezetimibe orally once a day for 12 weeks.
OG003
Evolocumab 70 mg Q2W
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG004
Evolocumab 105 mg Q2W
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Time Frame
12 weeks
Description
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Placebo Q2W
Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
0
45
10
45
EG001
Placebo Q4W
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
0
45
10
45
EG002
Ezetimibe
Participants received 10 mg ezetimibe orally once a day for 12 weeks.
0
45
14
45
EG003
Evolocumab 70 mg Q2W
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
0
45
11
45
EG004
Evolocumab 105 mg Q2W
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
1
46
11
46
EG005
Evolocumab 140 mg Q2W
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
1
45
14
45
EG006
Evolocumab 280 mg Q4W
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
0
45
7
45
EG007
Evolocumab 350 mg Q4W
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
1
45
11
45
EG008
Evolocumab 420 mg Q4W
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
0
45
9
45
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Appendicitis
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0000 affected45 at risk
EG0010 affected45 at risk
EG0020 affected45 at risk
EG0030 affected45 at risk
EG0040 affected46 at risk
EG0051 affected45 at risk
EG0060 affected45 at risk
EG0070 affected45 at risk
EG0080 affected45 at risk
Humerus fracture
Injury, poisoning and procedural complications
MedDRA 14.1
Systematic Assessment
EG0000 affected45 at risk
EG0010 affected45 at risk
EG0020 affected45 at risk
EG003
IgA nephropathy
Renal and urinary disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected45 at risk
EG0010 affected45 at risk
EG0020 affected45 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Diarrhoea
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected45 at risk
EG0013 affected45 at risk
EG0021 affected45 at risk
EG0032 affected45 at risk
EG0040 affected46 at risk
EG0052 affected45 at risk
EG0060 affected45 at risk
EG0073 affected45 at risk
EG0083 affected45 at risk
Nausea
Gastrointestinal disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected45 at risk
EG0011 affected45 at risk
EG0020 affected45 at risk
EG003
Fatigue
General disorders
MedDRA 14.1
Systematic Assessment
EG0003 affected45 at risk
EG0011 affected45 at risk
EG0022 affected45 at risk
EG003
Injection site induration
General disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected45 at risk
EG0010 affected45 at risk
EG0020 affected45 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0003 affected45 at risk
EG0010 affected45 at risk
EG0024 affected45 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 14.1
Systematic Assessment
EG0005 affected45 at risk
EG0012 affected45 at risk
EG0025 affected45 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 14.1
Systematic Assessment
EG0000 affected45 at risk
EG0014 affected45 at risk
EG0021 affected45 at risk
EG003
Headache
Nervous system disorders
MedDRA 14.1
Systematic Assessment
EG0003 affected45 at risk
EG0011 affected45 at risk
EG0021 affected45 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0002 affected45 at risk
EG0011 affected45 at risk
EG0021 affected45 at risk
EG003
Sinus congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 14.1
Systematic Assessment
EG0001 affected45 at risk
EG0011 affected45 at risk
EG0020 affected45 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
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.
Point of Contact
Title
Organization
Phone
Extension
Email
Study Director
Amgen Inc.
866-572-6436
ID
Term
D006949
Hyperlipidemias
D006937
Hypercholesterolemia
C566337
Hypercholesterolemia, Autosomal Dominant, 3
Ancestor Terms
ID
Term
D050171
Dyslipidemias
D052439
Lipid Metabolism Disorders
D008659
Metabolic Diseases
D009750
Nutritional and Metabolic Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
C577155
evolocumab
D000069438
Ezetimibe
Ancestor Terms
ID
Term
D001384
Azetidines
D001385
Azetines
D006573
Heterocyclic Compounds, 1-Ring
D006571
Heterocyclic Compounds
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
FG0050 subjects
FG0061 subjects
FG0070 subjects
FG0080 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0081 subjects
50.9
± 12.9
BG00448.3± 11.8
BG00552.8± 11.6
BG00649.3± 10.3
BG00750.9± 13.1
BG00850.1± 12.0
BG00950.6± 11.8
26
BG00330
BG00433
BG00536
BG00628
BG00733
BG00826
BG009267
Male
BG00020
BG00115
BG00219
BG00315
BG00413
BG0059
BG00617
BG00712
BG00819
BG009139
0
BG0031
BG0040
BG0050
BG0061
BG0071
BG0080
BG0093
Asian
Title
Measurements
BG0002
BG0011
BG0021
BG0033
BG0043
BG0052
BG0061
BG0072
BG0082
BG00917
Black or African American
Title
Measurements
BG0008
BG0017
BG0029
BG0037
BG0045
BG0054
BG0068
BG0076
BG00810
BG00964
Native Hawaiian or Other Pacific Islander
Title
Measurements
BG0000
BG0011
BG0020
BG0030
BG0041
BG0050
BG0060
BG0070
BG0080
BG0092
White
Title
Measurements
BG00035
BG00136
BG00235
BG00333
BG00437
BG00539
BG00635
BG00736
BG00833
BG009319
Other
Title
Measurements
BG0000
BG0010
BG0020
BG0031
BG0040
BG0050
BG0060
BG0070
BG0080
BG0091
5
BG0035
BG0045
BG0058
BG0067
BG0075
BG00810
BG00956
ot Hispanic or Latino
Title
Measurements
BG00040
BG00139
BG00240
BG00340
BG00441
BG00537
BG00638
BG00740
BG00835
BG009350
15
BG00314
BG00415
BG00514
BG00615
BG00715
BG00814
BG009131
≥ 130 mg/dL
Title
Measurements
BG00030
BG00131
BG00230
BG00331
BG00431
BG00531
BG00630
BG00730
BG00831
BG009275
144.2
± 25.8
BG003143.1± 21.7
BG004141.5± 22.3
BG005139.8± 21.1
BG006141.1± 21.8
BG007136.6± 20.8
BG008138.9± 21.9
BG009141.6± 22.3
170.0
± 32.0
BG003169.0± 24.5
BG004169.2± 24.3
BG005163.8± 23.7
BG006166.3± 27.8
BG007161.1± 26.1
BG008167.9± 29.6
BG009167.8± 27.4
109.9
± 17.7
BG003108.7± 15.7
BG004108.5± 15.2
BG005107.2± 16.3
BG006109.2± 15.7
BG007105.8± 15.9
BG008110.2± 18.4
BG009109.1± 16.5
4.670
± 1.258
BG0034.335± 1.090
BG0044.571± 1.269
BG0054.181± 1.131
BG0064.500± 1.154
BG0074.335± 1.282
BG0084.741± 1.656
BG0094.512± 1.351
0.752
± 0.176
BG0030.705± 0.161
BG0040.744± 0.168
BG0050.709± 0.175
BG0060.751± 0.161
BG0070.706± 0.185
BG0080.758± 0.191
BG0090.738± 0.196
45
OG00446
OG00545
OG00645
OG00745
OG00845
-40.98
± 2.64
OG004-43.87± 2.60
OG005-50.93± 2.66
OG006-39.02± 2.57
OG007-43.20± 2.57
OG008-47.98± 2.58
Superiority or Other (legacy)
OG000
OG004
The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
LS Mean Treatment Difference
-40.17
Standard Error of the Mean
3.66
95
-47.38
-32.95
Placebo is the reference
Superiority or Other (legacy)
OG000
OG003
The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
LS Mean Treatment Difference
-32.27
Standard Error of the Mean
3.68
2-Sided
95
-44.53
-30.02
Placebo is the reference
Superiority or Other (legacy)
OG001
OG008
The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
LS Mean Treatment Difference
-52.53
Standard Error of the Mean
3.62
2-Sided
95
-59.67
-45.38
Placebo is the reference
Superiority or Other (legacy)
OG001
OG007
The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
LS Mean Treatment Difference
-47.74
Standard Error of the Mean
3.62
2-Sided
95
-54.89
-40.60
Placebo is the reference
Superiority or Other (legacy)
OG001
OG006
The null hypothesis was that there was no mean difference in the percent change from Baseline at Week 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
LS Mean Treatment Difference
-43.57
Standard Error of the Mean
3.62
2-Sided
95
-50.71
-36.42
Placebo is the reference
Superiority or Other (legacy)
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG005
Evolocumab 140 mg Q2W
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG006
Evolocumab 280 mg Q4W
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG007
Evolocumab 350 mg Q4W
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG008
Evolocumab 420 mg Q4W
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Units
Counts
Participants
OG00045
OG00145
OG00245
OG00345
OG00446
OG00545
OG00645
OG00745
OG00845
Title
Denominators
Categories
Title
Measurements
OG000-3.4± 3.9
OG0017.3± 3.7
OG002-19.2± 3.6
OG003-55.7± 3.7
OG004-66.0± 3.7
OG005-69.3± 3.6
OG006-53.5± 3.6
OG007-56.7± 3.6
OG008-65.0± 3.6
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG005
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-65.9
Standard Error of the Mean
5.2
2-Sided
95
-76.3
-55.6
Placebo is the reference
Superiority or Other (legacy)
OG000
OG004
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-62.7
Standard Error of the Mean
5.3
95
-73.2
-52.2
Placebo is the reference
Superiority or Other (legacy)
OG000
OG003
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-52.3
Standard Error of the Mean
5.3
2-Sided
95
-62.7
-41.9
Placebo is the reference
Superiority or Other (legacy)
OG001
OG008
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-72.3
Standard Error of the Mean
5.0
2-Sided
95
-82.2
-62.4
Placebo is the reference
Superiority or Other (legacy)
OG001
OG007
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-63.9
Standard Error of the Mean
5.0
2-Sided
95
-73.9
-54.0
Placebo is the reference
Superiority or Other (legacy)
OG001
OG006
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-60.8
Standard Error of the Mean
5.0
2-Sided
95
-70.7
-50.9
Placebo is the reference
Superiority or Other (legacy)
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG005
Evolocumab 140 mg Q2W
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG006
Evolocumab 280 mg Q4W
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG007
Evolocumab 350 mg Q4W
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG008
Evolocumab 420 mg Q4W
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Units
Counts
Participants
OG00045
OG00145
OG00245
OG00345
OG00446
OG00545
OG00645
OG00745
OG00845
Title
Denominators
Categories
Title
Measurements
OG000-2.89± 2.40
OG001-0.25± 2.30
OG002-15.53± 2.36
OG003-37.95± 2.38
OG004-39.68± 2.34
OG005-48.04± 2.40
OG006-37.94± 2.24
OG007-42.14± 2.24
OG008-47.36± 2.25
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG005
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-45.15
Standard Error of the Mean
3.33
2-Sided
95
-51.72
-38.58
Placebo is the reference
Superiority or Other (legacy)
OG000
OG004
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-36.79
Standard Error of the Mean
3.29
95
-43.29
-30.29
Placebo is the reference
Superiority or Other (legacy)
OG000
OG003
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-35.06
Standard Error of the Mean
3.31
2-Sided
95
-41.59
-28.52
Placebo is the reference
Superiority or Other (legacy)
OG001
OG008
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-47.11
Standard Error of the Mean
3.15
2-Sided
95
-53.33
-40.89
Placebo is the reference
Superiority or Other (legacy)
OG001
OG007
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-41.89
Standard Error of the Mean
3.15
2-Sided
95
-48.11
-35.67
Placebo is the reference
Superiority or Other (legacy)
OG001
OG006
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-37.70
Standard Error of the Mean
3.15
2-Sided
95
-43.92
-31.47
Placebo is the reference
Superiority or Other (legacy)
OG005
Evolocumab 140 mg Q2W
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG006
Evolocumab 280 mg Q4W
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG007
Evolocumab 350 mg Q4W
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG008
Evolocumab 420 mg Q4W
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Units
Counts
Participants
OG00045
OG00145
OG00245
OG00345
OG00446
OG00545
OG00645
OG00745
OG00845
Title
Denominators
Categories
Title
Measurements
OG000-0.33± 2.28
OG0010.19± 2.28
OG002-11.17± 2.19
OG003-32.66± 2.26
OG004-36.20± 2.23
OG005-44.52± 2.28
OG006-33.04± 2.21
OG007-37.73± 2.21
OG008-42.29± 2.22
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG005
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-44.19
Standard Error of the Mean
3.17
2-Sided
95
-50.45
-37.94
Placebo is the reference
Superiority or Other (legacy)
OG000
OG004
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-35.87
Standard Error of the Mean
3.13
95
-42.06
-29.69
Placebo is the reference
Superiority or Other (legacy)
OG000
OG003
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-32.33
Standard Error of the Mean
3.15
2-Sided
95
-38.55
-26.11
Placebo is the reference
Superiority or Other (legacy)
OG001
OG008
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-42.48
Standard Error of the Mean
3.12
2-Sided
95
-48.63
-36.32
Placebo is the reference
Superiority or Other (legacy)
OG001
OG007
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-37.92
Standard Error of the Mean
3.12
2-Sided
95
-44.07
-31.76
Placebo is the reference
Superiority or Other (legacy)
OG001
OG006
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-33.22
Standard Error of the Mean
3.12
2-Sided
95
-39.38
-27.07
Placebo is the reference
Superiority or Other (legacy)
OG005
Evolocumab 140 mg Q2W
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG006
Evolocumab 280 mg Q4W
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG007
Evolocumab 350 mg Q4W
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG008
Evolocumab 420 mg Q4W
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Units
Counts
Participants
OG00045
OG00145
OG00245
OG00345
OG00446
OG00545
OG00645
OG00745
OG00845
Title
Denominators
Categories
Title
Measurements
OG000-1.21± 2.17
OG001-3.39± 2.11
OG002-16.65± 1.99
OG003-30.07± 2.15
OG004-33.13± 2.12
OG005-38.70± 2.17
OG006-32.07± 2.05
OG007-34.60± 2.05
OG008-39.97± 2.06
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG005
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-37.49
Standard Error of the Mean
3.01
2-Sided
95
-43.43
-31.54
Placebo is the reference
Superiority or Other (legacy)
OG000
OG004
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-31.92
Standard Error of the Mean
2.98
95
-37.79
-26.04
Placebo is the reference
Superiority or Other (legacy)
OG000
OG003
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-28.86
Standard Error of the Mean
2.99
2-Sided
95
-34.77
-22.95
Placebo is the reference
Superiority or Other (legacy)
OG001
OG008
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-36.58
Standard Error of the Mean
2.89
2-Sided
95
-42.29
-30.88
Placebo is the reference
Superiority or Other (legacy)
OG001
OG007
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-31.21
Standard Error of the Mean
2.89
2-Sided
95
-36.92
-25.51
Placebo is the reference
Superiority or Other (legacy)
OG001
OG006
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-28.69
Standard Error of the Mean
2.89
2-Sided
95
-34.39
-22.98
Placebo is the reference
Superiority or Other (legacy)
OG005
Evolocumab 140 mg Q2W
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG006
Evolocumab 280 mg Q4W
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG007
Evolocumab 350 mg Q4W
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG008
Evolocumab 420 mg Q4W
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Units
Counts
Participants
OG00045
OG00145
OG00245
OG00345
OG00446
OG00545
OG00645
OG00745
OG00845
Title
Denominators
Categories
Title
Measurements
OG0002.03± 2.40
OG0010.14± 2.46
OG002-12.35± 2.33
OG003-32.80± 2.38
OG004-38.30± 2.35
OG005-48.13± 2.40
OG006-36.10± 2.39
OG007-40.43± 2.39
OG008-45.33± 2.40
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG005
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-50.16
Standard Error of the Mean
3.34
2-Sided
95
-56.75
-43.58
Placebo is the reference
Superiority or Other (legacy)
OG000
OG004
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-40.33
Standard Error of the Mean
3.30
95
-46.84
-33.82
Placebo is the reference
Superiority or Other (legacy)
OG000
OG003
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-34.83
Standard Error of the Mean
3.32
2-Sided
95
-41.38
-28.28
Placebo is the reference
Superiority or Other (legacy)
OG001
OG008
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-45.47
Standard Error of the Mean
3.37
2-Sided
95
-52.12
-38.82
Placebo is the reference
Superiority or Other (legacy)
OG001
OG007
ANCOVA
The ANCOVA model included treatment group and the stratification factor.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-40.57
Standard Error of the Mean
3.37
2-Sided
95
-47.22
-33.92
Placebo is the reference
Superiority or Other (legacy)
OG001
OG006
ANCOVA
The ANCOVA model included treatment group and the stratification factor.