LAPLACE-TIMI 57: Low-density Lipoprotein Cholesterol (LDL-C) Assessment With PCSK9 monoclonaL Antibody Inhibition Combined With Statin thErapy
Official Title
LAPLACE TIMI 57 - A Double-blind, Randomized, Placebo-controlled, Multicenter, Dose-ranging Study to Evaluate Tolerability and Efficacy of AMG 145 on LDL-C in Combination With HMG-CoA Reductase Inhibitors in Hypercholesterolemic Subjects
Acronym
LAPLACE
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 1, 2011Actual
Primary Completion Date
Apr 5, 2012Actual
Completion Date
Apr 5, 2012Actual
First Submitted Date
Jun 23, 2011
First Submission Date that Met QC Criteria
Jun 23, 2011
First Posted Date
Jun 27, 2011Estimated
Results Waived
Not provided
Results First Submitted Date
Sep 1, 2015
Results First Submitted that Met QC Criteria
Sep 1, 2015
Results First Posted Date
Oct 1, 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 10, 2022
Last Update Posted Date
Nov 15, 2022Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
AmgenINDUSTRY
Collaborators
Name
Class
The TIMI Study Group
OTHER
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
To evaluate the effect of 12 weeks of subcutaneous (SC) evolocumab (AMG 145) administered every 2 weeks (Q2W) or every 4 weeks (Q4W), compared with placebo, on percent change from baseline in LDL-C when used in addition to a statin in adults with hypercholesterolemia.
Detailed Description
Not provided
Conditions Module
Conditions
Hyperlipidemia
Keywords
Hypercholesterolemia
Proprotein convertase subtilisin/kexin type 9 (PCSK9)
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
631Actual
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
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
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Biological: Evolocumab
Evolocumab 280 mg Q4W
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 ≤ 80 years of age
On an approved statin, with or without ezetimibe, with stable dose(s) for at least 4 weeks
Fasting LDL-C ≥ 85 mg/dL
Fasting triglycerides ≤ 400 mg/dL
Exclusion Criteria:
Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization
Type 1 diabetes; newly diagnosed or poorly controlled type 2 diabetes (Glycosyated Hemoglobin (HbA1c) > 8.5%)
Uncontrolled hypertension
New York Heart Association (NYHA) III or IV heart failure, or known left ventricular ejection fraction < 30%
Giugliano RP, Desai NR, Kohli P, Rogers WJ, Somaratne R, Huang F, Liu T, Mohanavelu S, Hoffman EB, McDonald ST, Abrahamsen TE, Wasserman SM, Scott R, Sabatine MS; LAPLACE-TIMI 57 Investigators. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet. 2012 Dec 8;380(9858):2007-17. doi: 10.1016/S0140-6736(12)61770-X. Epub 2012 Nov 6.
Eligible participants were randomized equally into 1 of 8 treatment groups. Randomization was stratified by screening LDL-C level (< 130 mg/dL or ≥ 130 mg/dL) and ezetimibe use at baseline (yes or no).
Recruitment Details
This study enrolled adults aged 18 - 80 years who were on a statin, with or without ezetimibe, with stable dose(s) for at least 4 weeks, and fasting low-density lipoprotein cholesterol (LDL-C) ≥ 85 mg/dL.
The first patient enrolled on 18 July 2011 and the last patient enrolled on 22 December 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.
Kohli P, Desai NR, Giugliano RP, Kim JB, Somaratne R, Huang F, Knusel B, McDonald S, Abrahamsen T, Wasserman SM, Scott R, Sabatine MS. Design and rationale of the LAPLACE-TIMI 57 trial: a phase II, double-blind, placebo-controlled study of the efficacy and tolerability of a monoclonal antibody inhibitor of PCSK9 in subjects with hypercholesterolemia on background statin therapy. Clin Cardiol. 2012;35(7):385-91. doi: 10.1002/clc.22014. Epub 2012 Jun 19.
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 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
Evolocumab 70 mg Q2W
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG003
Evolocumab 105 mg Q2W
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG004
Evolocumab 140 mg Q2W
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG005
Evolocumab 280 mg Q4W
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG006
Evolocumab 350 mg Q4W
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG007
Evolocumab 420 mg Q4W
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Units
Counts
Participants
OG00078
OG00177
OG00279
OG003
Title
Denominators
Categories
Title
Measurements
OG0002.76± 2.39
OG001-0.98± 2.51
OG002-39.06± 2.39
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
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 stratification factors.
<0.001
Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
LS Mean Treatment Difference
-66.10
Standard Error of the Mean
2.73
2-Sided
95
-71.48
-60.72
Placebo is the reference
Secondary
Change From Baseline in LDL-C at Week 12
LDL-C was measured using ultracentrifugation.
Full analysis set; missing data at Week 12 were 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
Evolocumab 70 mg Q2W
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG003
Evolocumab 105 mg Q2W
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG004
Evolocumab 140 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
Evolocumab 70 mg Q2W
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG003
Evolocumab 105 mg Q2W
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG004
Evolocumab 140 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
Evolocumab 70 mg Q2W
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG003
Evolocumab 105 mg Q2W
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG004
Evolocumab 140 mg Q2W
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
Evolocumab 70 mg Q2W
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG003
Evolocumab 105 mg Q2W
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG004
Evolocumab 140 mg Q2W
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
Evolocumab 70 mg Q2W
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG003
Evolocumab 105 mg Q2W
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG004
Evolocumab 140 mg Q2W
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.
4
78
15
78
EG001
Placebo Q4W
Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
0
77
17
77
EG002
Evolocumab 70 mg Q2W
Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
0
79
20
79
EG003
Evolocumab 105 mg Q2W
Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
1
79
28
79
EG004
Evolocumab 140 mg Q2W
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
4
78
27
78
EG005
Evolocumab 280 mg Q4W
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
2
79
21
79
EG006
Evolocumab 350 mg Q4W
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
2
79
23
79
EG007
Evolocumab 420 mg Q4W
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
2
80
30
80
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG0030 affected79 at risk
EG0041 affected78 at risk
EG0050 affected79 at risk
EG0060 affected79 at risk
EG0070 affected80 at risk
Atrial fibrillation
Cardiac disorders
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Cardiac failure congestive
Cardiac disorders
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Coronary artery disease
Cardiac disorders
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Pain
General disorders
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Cholecystitis acute
Hepatobiliary disorders
MedDRA 15.0
Systematic Assessment
EG0001 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 15.0
Systematic Assessment
EG0001 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Acetabulum fracture
Injury, poisoning and procedural complications
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Cervical vertebral fracture
Injury, poisoning and procedural complications
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Hand fracture
Injury, poisoning and procedural complications
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Joint dislocation
Injury, poisoning and procedural complications
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Laceration
Injury, poisoning and procedural complications
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Multiple injuries
Injury, poisoning and procedural complications
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Rib fracture
Injury, poisoning and procedural complications
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Road traffic accident
Injury, poisoning and procedural complications
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Spondylolisthesis
Musculoskeletal and connective tissue disorders
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Bladder cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 15.0
Systematic Assessment
EG0001 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Neurological symptom
Nervous system disorders
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Syncope
Nervous system disorders
MedDRA 15.0
Systematic Assessment
EG0001 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Alcohol withdrawal syndrome
Psychiatric disorders
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Delirium
Psychiatric disorders
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Substance abuse
Psychiatric disorders
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Penile haemorrhage
Reproductive system and breast disorders
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Chronic obstructive pulmonary disease
Respiratory, thoracic and mediastinal disorders
MedDRA 15.0
Systematic Assessment
EG0001 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Physical assault
Social circumstances
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Coronary artery bypass
Surgical and medical procedures
MedDRA 15.0
Systematic Assessment
EG0001 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Diarrhoea
Gastrointestinal disorders
MedDRA 15.0
Systematic Assessment
EG0002 affected78 at risk
EG0012 affected77 at risk
EG0021 affected79 at risk
EG0034 affected79 at risk
EG0042 affected78 at risk
EG0051 affected79 at risk
EG0062 affected79 at risk
EG0073 affected80 at risk
Nausea
Gastrointestinal disorders
MedDRA 15.0
Systematic Assessment
EG0001 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Fatigue
General disorders
MedDRA 15.0
Systematic Assessment
EG0001 affected78 at risk
EG0010 affected77 at risk
EG0020 affected79 at risk
EG003
Influenza
Infections and infestations
MedDRA 15.0
Systematic Assessment
EG0002 affected78 at risk
EG0011 affected77 at risk
EG0023 affected79 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 15.0
Systematic Assessment
EG0006 affected78 at risk
EG0015 affected77 at risk
EG0029 affected79 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 15.0
Systematic Assessment
EG0002 affected78 at risk
EG0012 affected77 at risk
EG0022 affected79 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0013 affected77 at risk
EG0024 affected79 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 15.0
Systematic Assessment
EG0001 affected78 at risk
EG0011 affected77 at risk
EG0020 affected79 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 15.0
Systematic Assessment
EG0000 affected78 at risk
EG0012 affected77 at risk
EG0022 affected79 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 15.0
Systematic Assessment
EG0001 affected78 at risk
EG0011 affected77 at risk
EG0020 affected79 at risk
EG003
Headache
Nervous system disorders
MedDRA 15.0
Systematic Assessment
EG0002 affected78 at risk
EG0010 affected77 at risk
EG0021 affected79 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 15.0
Systematic Assessment
EG0001 affected78 at risk
EG0012 affected77 at risk
EG0023 affected79 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
Ancestor Terms
Not provided
Browse Leaves
Not provided
Browse Branches
Not provided
58.8
± 9.7
BG00462.4± 10.2
BG00560.3± 8.4
BG00661.9± 8.8
BG00760.9± 10.3
BG00860.5± 9.5
44
BG00325
BG00445
BG00540
BG00638
BG00744
BG008319
Male
BG00036
BG00136
BG00235
BG00354
BG00433
BG00539
BG00641
BG00736
BG008310
0
BG0030
BG0041
BG0051
BG0060
BG0070
BG0083
Asian
Title
Measurements
BG0000
BG0012
BG0021
BG0033
BG0041
BG0052
BG0062
BG0071
BG00812
Black or African American
Title
Measurements
BG0006
BG0010
BG0026
BG0038
BG0049
BG0058
BG0064
BG0079
BG00850
Native Hawaiian or Other Pacific Islander
Title
Measurements
BG0000
BG0010
BG0020
BG0031
BG0040
BG0052
BG0060
BG0070
BG0083
White
Title
Measurements
BG00072
BG00174
BG00272
BG00367
BG00467
BG00564
BG00672
BG00770
BG008558
Other
Title
Measurements
BG0000
BG0010
BG0020
BG0030
BG0040
BG0052
BG0061
BG0070
BG0083
5
BG0030
BG0046
BG0051
BG0060
BG0072
BG00821
Not Hispanic or Latino
Title
Measurements
BG00077
BG00171
BG00274
BG00379
BG00472
BG00578
BG00679
BG00778
BG008608
51
BG00351
BG00452
BG00551
BG00652
BG00753
BG008412
≥ 130 mg/dL
Title
Measurements
BG00027
BG00126
BG00228
BG00328
BG00426
BG00528
BG00627
BG00727
BG008217
72
BG00372
BG00471
BG00572
BG00672
BG00773
BG008572
Yes
Title
Measurements
BG0007
BG0018
BG0027
BG0037
BG0047
BG0057
BG0067
BG0077
BG00857
121.4
± 24.4
BG003127.4± 32.1
BG004120.9± 25.1
BG005122.0± 28.8
BG006123.2± 27.1
BG007120.8± 26.5
BG008122.8± 27.7
145.3
± 29.9
BG003151.2± 37.2
BG004145.3± 26.2
BG005146.3± 33.3
BG006150.0± 29.1
BG007144.4± 31.2
BG008147.4± 31.8
99.9
± 16.8
BG003103.6± 22.3
BG00498.8± 16.6
BG005101.3± 21.2
BG006102.6± 18.9
BG00799.9± 18.6
BG008100.9± 19.0
4.002
± 1.243
BG0034.128± 1.473
BG0043.932± 1.022
BG0054.007± 1.300
BG0064.118± 0.963
BG0073.885± 1.090
BG0084.008± 1.184
0.675
± 0.191
BG0030.695± 0.219
BG0040.649± 0.155
BG0050.662± 0.199
BG0060.687± 0.175
BG0070.653± 0.177
BG0080.670± 0.184
79
OG00478
OG00579
OG00679
OG00780
-57.48
± 2.39
OG004-63.34± 2.40
OG005-42.82± 2.52
OG006-50.98± 2.51
OG007-51.31± 2.53
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 stratification factors.
<0.001
Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
LS Mean Treatment Difference
-60.24
Standard Error of the Mean
2.73
2-Sided
95
-65.61
-54.88
Placebo is the reference
Superiority or Other (legacy)
OG000
OG002
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 stratification factors.
<0.001
Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
LS Mean Treatment Difference
-41.82
Standard Error of the Mean
2.73
2-Sided
95
-47.18
-36.45
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 stratification factors.
<0.001
Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
LS Mean Treatment Difference
-50.33
Standard Error of the Mean
2.90
2-Sided
95
-56.04
-44.62
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 stratification factors.
<0.001
Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
LS Mean Treatment Difference
-50.00
Standard Error of the Mean
2.89
2-Sided
95
-55.69
-44.31
Placebo is the reference
Superiority or Other (legacy)
OG001
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 stratification factors.
<0.001
Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
LS Mean Treatment Difference
-41.84
Standard Error of the Mean
2.90
2-Sided
95
-47.55
-36.13
Placebo is the reference
Superiority or Other (legacy)
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG005
Evolocumab 280 mg Q4W
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG006
Evolocumab 350 mg Q4W
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG007
Evolocumab 420 mg Q4W
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Units
Counts
Participants
OG00078
OG00177
OG00279
OG00379
OG00478
OG00579
OG00679
OG00780
Title
Denominators
Categories
Title
Measurements
OG000-0.2± 3.4
OG001-3.2± 3.3
OG002-50.9± 3.4
OG003-77.6± 3.5
OG004-79.5± 3.4
OG005-53.7± 3.3
OG006-64.3± 3.3
OG007-64.3± 3.3
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
OG004
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-79.2
Standard Error of the Mean
4.0
2-Sided
95
-87.0
-71.5
Placebo is the reference
Superiority or Other (legacy)
OG000
OG003
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-77.4
Standard Error of the Mean
4.0
2-Sided
95
-85.2
-69.6
Placebo is the reference
Superiority or Other (legacy)
OG000
OG002
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-50.7
Standard Error of the Mean
4.0
2-Sided
95
-58.5
-43.0
Placebo is the reference
Superiority or Other (legacy)
OG001
OG007
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-61.1
Standard Error of the Mean
3.8
2-Sided
95
-68.6
-53.7
Placebo is the reference
Superiority or Other (legacy)
OG001
OG006
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-61.1
Standard Error of the Mean
3.8
2-Sided
95
-68.5
-53.7
Placebo is the reference
Superiority or Other (legacy)
OG001
OG005
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-50.6
Standard Error of the Mean
3.8
2-Sided
95
-58.0
-43.1
Placebo is the reference
Superiority or Other (legacy)
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG005
Evolocumab 280 mg Q4W
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG006
Evolocumab 350 mg Q4W
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG007
Evolocumab 420 mg Q4W
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Units
Counts
Participants
OG00078
OG00177
OG00279
OG00379
OG00478
OG00579
OG00679
OG00780
Title
Denominators
Categories
Title
Measurements
OG0002.21± 2.20
OG001-1.26± 2.26
OG002-36.23± 2.20
OG003-53.21± 2.20
OG004-59.19± 2.21
OG005-39.05± 2.27
OG006-47.05± 2.26
OG007-48.83± 2.27
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
OG004
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-61.40
Standard Error of the Mean
2.53
2-Sided
95
-66.37
-56.43
Placebo is the reference
Superiority or Other (legacy)
OG000
OG003
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-55.42
Standard Error of the Mean
2.52
2-Sided
95
-60.37
-50.47
Placebo is the reference
Superiority or Other (legacy)
OG000
OG002
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-38.44
Standard Error of the Mean
2.52
2-Sided
95
-43.39
-33.48
Placebo is the reference
Superiority or Other (legacy)
OG001
OG007
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-47.58
Standard Error of the Mean
2.61
2-Sided
95
-52.72
-42.44
Placebo is the reference
Superiority or Other (legacy)
OG001
OG006
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-45.80
Standard Error of the Mean
2.60
2-Sided
95
-50.92
-40.67
Placebo is the reference
Superiority or Other (legacy)
OG001
OG005
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-37.79
Standard Error of the Mean
2.61
2-Sided
95
-42.94
-32.65
Placebo is the reference
Superiority or Other (legacy)
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG005
Evolocumab 280 mg Q4W
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG006
Evolocumab 350 mg Q4W
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG007
Evolocumab 420 mg Q4W
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Units
Counts
Participants
OG00078
OG00177
OG00279
OG00379
OG00478
OG00579
OG00679
OG00780
Title
Denominators
Categories
Title
Measurements
OG0005.86± 2.15
OG0013.22± 2.25
OG002-28.88± 2.15
OG003-44.29± 2.14
OG004-50.59± 2.15
OG005-31.16± 2.26
OG006-37.55± 2.26
OG007-38.81± 2.27
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
OG004
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-56.45
Standard Error of the Mean
2.46
2-Sided
95
-61.28
-51.61
Placebo is the reference
Superiority or Other (legacy)
OG000
OG003
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-50.15
Standard Error of the Mean
2.45
2-Sided
95
-54.97
-45.33
Placebo is the reference
Superiority or Other (legacy)
OG000
OG002
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-34.74
Standard Error of the Mean
2.45
2-Sided
95
-39.56
-29.92
Placebo is the reference
Superiority or Other (legacy)
OG001
OG007
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-42.03
Standard Error of the Mean
2.61
2-Sided
95
-47.16
-36.90
Placebo is the reference
Superiority or Other (legacy)
OG001
OG006
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-40.77
Standard Error of the Mean
2.60
2-Sided
95
-45.88
-35.66
Placebo is the reference
Superiority or Other (legacy)
OG001
OG005
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-34.38
Standard Error of the Mean
2.61
2-Sided
95
-39.51
-29.25
Placebo is the reference
Superiority or Other (legacy)
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG005
Evolocumab 280 mg Q4W
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG006
Evolocumab 350 mg Q4W
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG007
Evolocumab 420 mg Q4W
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Units
Counts
Participants
OG00078
OG00177
OG00279
OG00379
OG00478
OG00579
OG00679
OG00780
Title
Denominators
Categories
Title
Measurements
OG0002.64± 1.97
OG001-2.00± 1.90
OG002-28.76± 1.97
OG003-40.73± 1.97
OG004-45.09± 1.98
OG005-29.73± 1.91
OG006-37.97± 1.91
OG007-37.66± 1.92
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
OG004
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-47.74
Standard Error of the Mean
2.26
2-Sided
95
-52.18
-43.29
Placebo is the reference
Superiority or Other (legacy)
OG000
OG003
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-43.38
Standard Error of the Mean
2.25
2-Sided
95
-47.81
-38.94
Placebo is the reference
Superiority or Other (legacy)
OG000
OG002
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-31.40
Standard Error of the Mean
2.25
2-Sided
95
-35.83
-26.97
Placebo is the reference
Superiority or Other (legacy)
OG001
OG007
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-35.65
Standard Error of the Mean
2.20
2-Sided
95
-39.99
-31.32
Placebo is the reference
Superiority or Other (legacy)
OG001
OG006
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-35.97
Standard Error of the Mean
2.20
2-Sided
95
-40.29
-31.65
Placebo is the reference
Superiority or Other (legacy)
OG001
OG005
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-27.73
Standard Error of the Mean
2.20
2-Sided
95
-32.06
-23.39
Placebo is the reference
Superiority or Other (legacy)
Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
OG005
Evolocumab 280 mg Q4W
Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG006
Evolocumab 350 mg Q4W
Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
OG007
Evolocumab 420 mg Q4W
Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Units
Counts
Participants
OG00078
OG00177
OG00279
OG00379
OG00478
OG00579
OG00679
OG00780
Title
Denominators
Categories
Title
Measurements
OG000-0.30± 2.13
OG001-0.35± 2.38
OG002-35.04± 2.13
OG003-47.60± 2.12
OG004-53.73± 2.14
OG005-34.11± 2.40
OG006-42.74± 2.39
OG007-43.28± 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
OG004
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-53.44
Standard Error of the Mean
2.44
2-Sided
95
-58.23
-48.65
Placebo is the reference
Superiority or Other (legacy)
OG000
OG003
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-47.30
Standard Error of the Mean
2.43
2-Sided
95
-52.08
-42.52
Placebo is the reference
Superiority or Other (legacy)
OG000
OG002
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-34.75
Standard Error of the Mean
2.43
2-Sided
95
-39.53
-29.97
Placebo is the reference
Superiority or Other (legacy)
OG001
OG007
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-42.93
Standard Error of the Mean
2.76
2-Sided
95
-48.36
-37.50
Placebo is the reference
Superiority or Other (legacy)
OG001
OG006
ANCOVA
The ANCOVA model included treatment group and stratification factors.
<0.001
Testing based on a significance level of 0.05.
LS Mean Treatment Difference
-42.40
Standard Error of the Mean
2.75
2-Sided
95
-47.81
-36.98
Placebo is the reference
Superiority or Other (legacy)
OG001
OG005
ANCOVA
The ANCOVA model included treatment group and stratification factors.