Study of Evinacumab (REGN1500) in Participants With Persi... | NCT03175367

ID	Type	Description	Link
2017-001508-31	EudraCT Number

Study of Evinacumab (REGN1500) in Participants With Persi... | NCT03175367 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Group A: dosing regimen 1	Experimental	SC Evinacumab QW for 16 weeks	Drug: Evinacumab Other: Background Lipid Modifying Therapy (LMT)
Group A: dosing regimen 2	Experimental	SC Evinacumab Q2W for 16 weeks (alternating with matching placebo on opposite weeks)	Drug: Evinacumab Other: Background Lipid Modifying Therapy (LMT)
Group A: dosing regimen 3	Experimental	SC Evinacumab QW for 16 weeks	Drug: Evinacumab Other: Background Lipid Modifying Therapy (LMT)
Group A: matching placebo	Experimental	Placebo SC QW for 16 weeks	Drug: Matching placebo Other: Background Lipid Modifying Therapy (LMT)
Group B: dosing regimen 1	Experimental	Intravenous (IV) Evinacumab Q4W for 24 weeks	Drug: Evinacumab Other: Background Lipid Modifying Therapy (LMT)
Group B: dosing regimen 2

Name	Type	Description	Arm Group Labels	Other Names
Evinacumab	Drug	SC or IV administration	Group A: dosing regimen 1 Group A: dosing regimen 2 Group A: dosing regimen 3 Group B: dosing regimen 1

Outcomes Module

Measure	Description	Time Frame
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 16 (Intent-to-Treat [ITT] Estimand)		Baseline and Week 16

Secondary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 (ITT Estimand)		Baseline and Week 16
Percent Change From Baseline in Apo B at Week 24 (ITT Estimand)		Baseline and Week 24

Eligibility Module

Eligibility Criteria

The inclusion/ exclusion criteria below, include, but are not limited to, the following:

Key Inclusion Criteria:

Men and women, ages 18 through 80 at the screening visit
Diagnosis of primary hypercholesterolemia, either HeFH or non-HeFH with clinical ASCVD
A history of clinical ASCVD, for those patients who are non-HeFH.
Receiving a stable maximally tolerated statin (± ezetimibe) for at least 4 weeks at screening
For those patients with HeFH who are not receiving a statin at screening, documentation of inability to tolerate at least 2 statins.
Receiving alirocumab 150 mg SC Q2W, OR evolocumab 140 mg SC Q2W or 420 mg SC Q4W for at least 8 weeks prior to the screening visit
For those patients with a history of clinical ASCVD, serum LDL-C ≥ 70 mg/dL at screening (1 repeat lab is allowed)
For those patients without a history of clinical ASCVD, serum LDL-C ≥ 100 mg/dL at screening (1 repeat lab is allowed)
Provide signed informed consent

Key Exclusion Criteria:

Known history of homozygous FH (clinically, or by previous genotyping)
Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
Newly diagnosed diabetes (within 3 months prior to screening)
Use of thyroid medications (except for replacement therapy which has been stable for at least 12 weeks before screening)
Laboratory findings during screening period (not including randomization labs):
1. Triglycerides > 400 mg/dL (> 4.52 mmol/L) for patients without a known history of diabetes mellitus; OR Triglycerides > 300 mg/dL (> 3.39 mmol/L) for patients with a known history of diabetes mellitus
2. Positive test for Hepatitis B surface antigen and/or Hepatitis C antibody (associated with a positive HCV ribonucleic acid [RNA] polymerase chain reaction)
3. Positive serum beta-human chorionic gonadotropin or urine pregnancy test in women of childbearing potential
4. Estimated glomerular filtration rate < 30 mL/min/1.73 m^2
5. TSH > 1.5 x ULN
6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 x ULN
Systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg at screening visit or time of randomization
History of heart failure (New York Heart Association [NYHA] Class III-IV) within 12 months before screening
History of MI, unstable angina leading to hospitalization, CABG surgery, PCI, uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, TIA, carotid revascularization, endovascular procedure or surgical intervention for peripheral vascular disease within 3 months prior screening
History of cancer within the past 5 years (except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer)
Having received LDL apheresis within 2 months before screening
Pregnant or breast-feeding women
Women of childbearing potential who are unwilling to practice a highly effective birth control method
Men who are sexually active with women of childbearing potential (WOCBP) and are unwilling to consistently use condoms during the study drug treatment period regardless of vasectomy status.

Contacts/Locations Module

Name	Affiliation	Role
Clinical Trial Management	Regeneron Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Cedars-Sinai Medical Center		Los Angeles	California	90048	United States
Office of Dr. John D Homan MD

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37703006	Derived	Rosenson RS, Burgess LJ, Ebenbichler CF, Baum SJ, Stroes ESG, Ali S, Khilla N, McGinniss J, Gaudet D, Pordy R. Longer-Term Efficacy and Safety of Evinacumab in Patients With Refractory Hypercholesterolemia. JAMA Cardiol. 2023 Nov 1;8(11):1070-1076. doi: 10.1001/jamacardio.2023.2921.
33196153	Derived	Rosenson RS, Burgess LJ, Ebenbichler CF, Baum SJ, Stroes ESG, Ali S, Khilla N, Hamlin R, Pordy R, Dong Y, Son V, Gaudet D. Evinacumab in Patients with Refractory Hypercholesterolemia. N Engl J Med. 2020 Dec 10;383(24):2307-2319. doi: 10.1056/NEJMoa2031049. Epub 2020 Nov 15.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Group A: Placebo SC QW (DBTP)	Placebo subcutaneous (SC) treatment every week (QW) for 16 weeks during the double-blind treatment period (DBTP) followed by a 23-week follow-up period
FG001	Group A: Evinacumab 300 mg SC Q2W (DBTP)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 11, 2019	Dec 19, 2022

Type	Comment	Reasons
Protocol Violation		FG0000 subjects FG0010 subjects FG0021 subjects FG0032 subjects FG0040 subjects FG0050 subjects FG0062 subjects
Adverse Event		FG0002 subjects FG0012 subjects FG0020 subjects FG0030 subjects FG004
Withdrawal by Subject		FG0001 subjects FG0011 subjects FG0022 subjects FG0032 subjects FG004
Physician Decision		FG0006 subjects FG0015 subjects FG0028 subjects FG0036 subjects FG004
Lost to Follow-up		FG0000 subjects FG0010 subjects FG0021 subjects FG0030 subjects FG004

Open-Label Treatment Period (OLTP)

Type	Comment	Milestone Data
STARTED	Treated in OLTP	FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG00431 subjects FG00532 subjects FG00633 subjectsOne participant completed DBTP, but did not continue to OLTP
COMPLETED	Completed Study	FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004

Type	Comment	Reasons
Noncompliance with protocol		FG0000 subjects FG0010 subjects FG0020 subjects FG003

Arm/Group Information

ID	Title	Description
BG000	Group A: Placebo SC QW (DBTP)	Placebo subcutaneous (SC) treatment every week (QW) for 16 weeks during the double-blind treatment period (DBTP) followed by a 23-week follow-up period
BG001	Group A: Evinacumab 300 mg SC Q2W (DBTP)	Evinacumab 300 mg SC treatment every other week (Q2W) (alternating with placebo on opposite weeks) for 16 weeks during the DBTP followed by a 23-week follow-up period
BG002	Group A: Evinacumab 300 mg SC QW (DBTP)	Evinacumab 300 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
BG003	Group A: Evinacumab 450 mg SC QW (DBTP)	Evinacumab 450 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
BG004	Group B: Placebo IV Q4W (DBTP to OLTP)	Placebo intravenous (IV) treatment every 4 weeks (Q4W) during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week open-label treatment period (OLTP) regardless of treatment assignment in the DBTP
BG005	Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP)	Evinacumab 5 mg/kg IV treatment Q4W during the 24-week DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP
BG006	Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP)	Evinacumab 15 mg/kg IV treatment Q4W during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP
BG007	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Customized

Number

Participants

Title

Denominators

Categories

Adults (18-64 years)

Title	Measurements
	BG00034 BG00129 BG00234 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00027 BG00121 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0002 BG0015 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 16 (Intent-to-Treat [ITT] Estimand)

Posted

Least Squares Mean

Standard Error

Percent Change

Baseline and Week 16

ID	Title	Description
OG000	Group A: Placebo SC QW (DBTP)	Placebo subcutaneous (SC) treatment every week (QW) for 16 weeks during the double-blind treatment period (DBTP) followed by a 23-week follow-up period
OG001	Group A: Evinacumab 300 mg SC Q2W (DBTP)	Evinacumab 300 mg SC treatment every other week (Q2W) (alternating with placebo on opposite weeks) for 16 weeks during the DBTP followed by a 23-week follow-up period
OG002	Group A: Evinacumab 300 mg SC QW (DBTP)	Evinacumab 300 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
OG003	Group A: Evinacumab 450 mg SC QW (DBTP)	Evinacumab 450 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
OG004	Group B: Placebo IV Q4W (DBTP to OLTP)	Placebo intravenous (IV) treatment every 4 weeks (Q4W) during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week open-label treatment period (OLTP) regardless of treatment assignment in the DBTP
OG005	Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP)	Evinacumab 5 mg/kg IV treatment Q4W during the 24-week DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP
OG006	Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP)	Evinacumab 15 mg/kg IV treatment Q4W during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP

Units	Counts
Participants	OG00039 OG00139 OG00242 OG003

Title

Denominators

Categories

Title	Measurements
	OG0008.8± 6.4(6.4 to ) OG001-29.7± 6.4(6.4 to ) OG002-44.0± 6.3(6.3 to )

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 OG001		Mixed Models Analysis		< .0001		Least Squares Mean Difference	-38.5	Standard Error of the Mean	9.1	2-Sided	95	-56.5	-20.6					Superiority
OG000 OG002		Mixed Models Analysis

Secondary

Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16 (ITT Estimand)

Posted

Least Squares Mean

Standard Error

Percent Change

Baseline and Week 16

ID	Title	Description
OG000	Group A: Placebo SC QW (DBTP)	Placebo subcutaneous (SC) treatment every week (QW) for 16 weeks during the double-blind treatment period (DBTP) followed by a 23-week follow-up period
OG001	Group A: Evinacumab 300 mg SC Q2W (DBTP)	Evinacumab 300 mg SC treatment every other week (Q2W) (alternating with placebo on opposite weeks) for 16 weeks during the DBTP followed by a 23-week follow-up period
OG002	Group A: Evinacumab 300 mg SC QW (DBTP)	Evinacumab 300 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
OG003	Group A: Evinacumab 450 mg SC QW (DBTP)	Evinacumab 450 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
OG004	Group B: Placebo IV Q4W (DBTP to OLTP)

Secondary

Percent Change From Baseline in Apo B at Week 24 (ITT Estimand)

Posted

Least Squares Mean

Standard Error

Percent Change

Baseline and Week 24

ID	Title	Description
OG000	Group B: Placebo IV Q4W (DBTP to OLTP)	Placebo intravenous (IV) treatment every 4 weeks (Q4W) during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week open-label treatment period (OLTP) regardless of treatment assignment in the DBTP
OG001	Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP)	Evinacumab 5 mg/kg IV treatment Q4W during the 24-week DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP
OG002	Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP)	Evinacumab 15 mg/kg IV treatment Q4W during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP

Units	Counts
Participants

Secondary

Percent Change From Baseline in Non High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16 (ITT Estimand)

Posted

Least Squares Mean

Standard Error

Percent Change

Baseline and Week 16

ID	Title	Description
OG000	Group A: Placebo SC QW (DBTP)	Placebo subcutaneous (SC) treatment every week (QW) for 16 weeks during the double-blind treatment period (DBTP) followed by a 23-week follow-up period
OG001	Group A: Evinacumab 300 mg SC Q2W (DBTP)	Evinacumab 300 mg SC treatment every other week (Q2W) (alternating with placebo on opposite weeks) for 16 weeks during the DBTP followed by a 23-week follow-up period
OG002	Group A: Evinacumab 300 mg SC QW (DBTP)	Evinacumab 300 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
OG003	Group A: Evinacumab 450 mg SC QW (DBTP)	Evinacumab 450 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
OG004

Secondary

Percent Change From Baseline in Non-HDL-C at Week 24 (ITT Estimand)

Posted

Least Squares Mean

Standard Error

Percent Change

Baseline and Week 24

ID	Title	Description
OG000	Group B: Placebo IV Q4W (DBTP to OLTP)	Placebo intravenous (IV) treatment every 4 weeks (Q4W) during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week open-label treatment period (OLTP) regardless of treatment assignment in the DBTP
OG001	Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP)	Evinacumab 5 mg/kg IV treatment Q4W during the 24-week DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP
OG002	Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP)	Evinacumab 15 mg/kg IV treatment Q4W during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP

Units	Counts
Participants

Secondary

Percentage of Participants With >= 30% Reduction in Calculated LDL-C at Week 16 (ITT Estimand)

Posted

Number

Percentage of Participants

Week 16

ID	Title	Description
OG000	Group A: Placebo SC QW (DBTP)	Placebo subcutaneous (SC) treatment every week (QW) for 16 weeks during the double-blind treatment period (DBTP) followed by a 23-week follow-up period
OG001	Group A: Evinacumab 300 mg SC Q2W (DBTP)	Evinacumab 300 mg SC treatment every other week (Q2W) (alternating with placebo on opposite weeks) for 16 weeks during the DBTP followed by a 23-week follow-up period
OG002	Group A: Evinacumab 300 mg SC QW (DBTP)	Evinacumab 300 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
OG003	Group A: Evinacumab 450 mg SC QW (DBTP)	Evinacumab 450 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
OG004	Group B: Placebo IV Q4W (DBTP to OLTP)

Secondary

Percentage of Participants With >= 50% Reduction in Calculated LDL-C at Week 16 (ITT Estimand)

Posted

Number

Percentage of Participants

Week 16

ID	Title	Description
OG000	Group A: Placebo SC QW (DBTP)	Placebo subcutaneous (SC) treatment every week (QW) for 16 weeks during the double-blind treatment period (DBTP) followed by a 23-week follow-up period
OG001	Group A: Evinacumab 300 mg SC Q2W (DBTP)	Evinacumab 300 mg SC treatment every other week (Q2W) (alternating with placebo on opposite weeks) for 16 weeks during the DBTP followed by a 23-week follow-up period
OG002	Group A: Evinacumab 300 mg SC QW (DBTP)	Evinacumab 300 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
OG003	Group A: Evinacumab 450 mg SC QW (DBTP)	Evinacumab 450 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
OG004	Group B: Placebo IV Q4W (DBTP to OLTP)

Secondary

Percentage of Participants With Calculated LDL-C < 50 mg/dL (1.30 mmol/L) at Week 16 (ITT Estimand)

Percentage of Participants with Calculated LDL-C < 50 milligrams/deciliter (mg/dL) [1.30 Millimoles per liter (mmol/L)] at Week 16 (ITT Estimand)

Posted

Number

Percentage of Participants

Week 16

ID	Title	Description
OG000	Group A: Placebo SC QW (DBTP)	Placebo subcutaneous (SC) treatment every week (QW) for 16 weeks during the double-blind treatment period (DBTP) followed by a 23-week follow-up period
OG001	Group A: Evinacumab 300 mg SC Q2W (DBTP)	Evinacumab 300 mg SC treatment every other week (Q2W) (alternating with placebo on opposite weeks) for 16 weeks during the DBTP followed by a 23-week follow-up period
OG002	Group A: Evinacumab 300 mg SC QW (DBTP)	Evinacumab 300 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
OG003	Group A: Evinacumab 450 mg SC QW (DBTP)	Evinacumab 450 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period

Secondary

Percent Change From Baseline in Calculated LDL-C at Week 24 (ITT Estimand)

Posted

Least Squares Mean

Standard Error

Percent Change

Baseline and Week 24

ID	Title	Description
OG000	Group B: Placebo IV Q4W (DBTP to OLTP)	Placebo intravenous (IV) treatment every 4 weeks (Q4W) during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week open-label treatment period (OLTP) regardless of treatment assignment in the DBTP
OG001	Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP)	Evinacumab 5 mg/kg IV treatment Q4W during the 24-week DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP
OG002	Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP)	Evinacumab 15 mg/kg IV treatment Q4W during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP

Units	Counts
Participants

Secondary

Percent Change From Baseline in Total Cholesterol (TC) at Week 16 (ITT Estimand)

Posted

Least Squares Mean

Standard Error

Percent Change

Baseline and Week 16

ID	Title	Description
OG000	Group A: Placebo SC QW (DBTP)	Placebo subcutaneous (SC) treatment every week (QW) for 16 weeks during the double-blind treatment period (DBTP) followed by a 23-week follow-up period
OG001	Group A: Evinacumab 300 mg SC Q2W (DBTP)	Evinacumab 300 mg SC treatment every other week (Q2W) (alternating with placebo on opposite weeks) for 16 weeks during the DBTP followed by a 23-week follow-up period
OG002	Group A: Evinacumab 300 mg SC QW (DBTP)	Evinacumab 300 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
OG003	Group A: Evinacumab 450 mg SC QW (DBTP)	Evinacumab 450 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
OG004	Group B: Placebo IV Q4W (DBTP to OLTP)

Secondary

Percent Change From Baseline in Total Cholesterol at Week 24 (ITT Estimand)

Posted

Least Squares Mean

Standard Error

Percent Change

Baseline and Week 24

ID	Title	Description
OG000	Group B: Placebo IV Q4W (DBTP to OLTP)	Placebo intravenous (IV) treatment every 4 weeks (Q4W) during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week open-label treatment period (OLTP) regardless of treatment assignment in the DBTP
OG001	Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP)	Evinacumab 5 mg/kg IV treatment Q4W during the 24-week DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP
OG002	Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP)	Evinacumab 15 mg/kg IV treatment Q4W during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP

Units	Counts
Participants

Secondary

Percent Change From Baseline in Fasting Triglycerides at Week 16 (ITT Estimand)

Posted

Least Squares Mean

Standard Error

Percent Change

Baseline and Week 16

ID	Title	Description
OG000	Group A: Placebo SC QW (DBTP)	Placebo subcutaneous (SC) treatment every week (QW) for 16 weeks during the double-blind treatment period (DBTP) followed by a 23-week follow-up period
OG001	Group A: Evinacumab 300 mg SC Q2W (DBTP)	Evinacumab 300 mg SC treatment every other week (Q2W) (alternating with placebo on opposite weeks) for 16 weeks during the DBTP followed by a 23-week follow-up period
OG002	Group A: Evinacumab 300 mg SC QW (DBTP)	Evinacumab 300 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
OG003	Group A: Evinacumab 450 mg SC QW (DBTP)	Evinacumab 450 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
OG004	Group B: Placebo IV Q4W (DBTP to OLTP)

Secondary

Percent Change From Baseline in Fasting Triglycerides at Week 24 (ITT Estimand)

Posted

Least Squares Mean

Standard Error

Percent Change

Baseline and Week 24

ID	Title	Description
OG000	Group B: Placebo IV Q4W (DBTP to OLTP)	Placebo intravenous (IV) treatment every 4 weeks (Q4W) during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week open-label treatment period (OLTP) regardless of treatment assignment in the DBTP
OG001	Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP)	Evinacumab 5 mg/kg IV treatment Q4W during the 24-week DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP
OG002	Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP)	Evinacumab 15 mg/kg IV treatment Q4W during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP

Units	Counts
Participants

Secondary

Percent Change From Baseline in Lipoprotein a [Lp(a)] at Week 16 (ITT Estimand)

Posted

Least Squares Mean

Standard Error

Percent Change

Baseline and Week 16

ID	Title	Description
OG000	Group A: Placebo SC QW (DBTP)	Placebo subcutaneous (SC) treatment every week (QW) for 16 weeks during the double-blind treatment period (DBTP) followed by a 23-week follow-up period
OG001	Group A: Evinacumab 300 mg SC Q2W (DBTP)	Evinacumab 300 mg SC treatment every other week (Q2W) (alternating with placebo on opposite weeks) for 16 weeks during the DBTP followed by a 23-week follow-up period
OG002	Group A: Evinacumab 300 mg SC QW (DBTP)	Evinacumab 300 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
OG003	Group A: Evinacumab 450 mg SC QW (DBTP)	Evinacumab 450 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period
OG004	Group B: Placebo IV Q4W (DBTP to OLTP)

Secondary

Percent Change From Baseline in Lipoprotein (a) [Lp(a)] at Week 24 (ITT Estimand)

Posted

Least Squares Mean

Standard Error

Percent Change

Baseline and Week 24

ID	Title	Description
OG000	Group B: Placebo IV Q4W (DBTP to OLTP)	Placebo intravenous (IV) treatment every 4 weeks (Q4W) during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week open-label treatment period (OLTP) regardless of treatment assignment in the DBTP
OG001	Group B: Evinacumab 5 mg/kg IV Q4W (DBTP to OLTP)	Evinacumab 5 mg/kg IV treatment Q4W during the 24-week DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP
OG002	Group B: Evinacumab 15 mg/kg IV Q4W (DBTP to OLTP)	Evinacumab 15 mg/kg IV treatment Q4W during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP

Units	Counts
Participants

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	Group A: Placebo SC QW (DBTP)	Placebo subcutaneous (SC) treatment every week (QW) for 16 weeks during the double-blind treatment period (DBTP) followed by a 23-week follow-up period	0	39	3	39	20	39
EG001	Group A: Evinacumab 300 mg SC Q2W (DBTP)	Evinacumab 300 mg SC treatment every other week (Q2W) (alternating with placebo on opposite weeks) for 16 weeks during the DBTP followed by a 23-week follow-up period	1	39	2	39	27	39
EG002	Group A: Evinacumab 300 mg SC QW (DBTP)	Evinacumab 300 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period	1	42	4	42	26	42
EG003	Group A: Evinacumab 450 mg SC QW (DBTP)	Evinacumab 450 mg SC treatment QW for 16 weeks during the DBTP followed by a 23-week follow-up period	0	40	4	40	22	40
EG004	Group B: Placebo IV Q4W (DBTP)	Placebo intravenous (IV) treatment every 4 weeks (Q4W) during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week open-label treatment period (OLTP) regardless of treatment assignment in the DBTP	0	33	1	33	18	33
EG005	Group B: Evinacumab 5 mg/kg IV Q4W (DBTP)	Evinacumab 5 mg/kg IV treatment Q4W during the 24-week DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP	0	36	2	36	23	36
EG006	Group B: Evinacumab 15 mg/kg IV Q4W (DBTP)	Evinacumab 15 mg/kg IV treatment Q4W during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP	0	37	6	37	24	37
EG007	Group B: Placebo IV Q4W (OLTP)	Placebo intravenous (IV) treatment every 4 weeks (Q4W) during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week open-label treatment period (OLTP) regardless of treatment assignment in the DBTP	0	31	4	31	19	31
EG008	Group B: Evinacumab 5 mg/kg IV Q4W (OLTP)	Evinacumab 5 mg/kg IV treatment Q4W during the 24-week DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP	0	32	3	32	22	32
EG009	Group B: Evinacumab 15 mg/kg IV Q4W (OLTP)	Evinacumab 15 mg/kg IV treatment Q4W during the DBTP followed by evinacumab 15 mg/kg IV Q4W for a 48-week OLTP regardless of treatment assignment in the DBTP	0	33	2	33	24	33

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG0030 events0 affected40 at risk EG004
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected39 at risk EG0020 events0 affected42 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0021 events1 affected42 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Palpitations	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events1 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Gastrointestinal motility disorder	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Hiatus hernia	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events1 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Chest pain	General disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
General physical health deterioration	General disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0021 events1 affected42 at risk EG003
Gallbladder polyp	Hepatobiliary disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Anaphylactic reaction	Immune system disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Appendicitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Corona virus infection	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Rib fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Tendon rupture	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Tibia fracture	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Joint effusion	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Bladder transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0021 events1 affected42 at risk EG003
Glioblastoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Carotid artery stenosis	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Hypertensive encephalopathy	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Ischaemic stroke	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected39 at risk EG0020 events0 affected42 at risk EG003
Seizure	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events1 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Syncope	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0021 events1 affected42 at risk EG003
Urinary bladder polyp	Renal and urinary disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0021 events1 affected42 at risk EG003
Acquired hydrocele	Reproductive system and breast disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Peripheral arterial occlusive disease	Vascular disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0015 events4 affected39 at risk EG0023 events1 affected42 at risk EG0032 events2 affected40 at risk EG0045 events4 affected33 at risk EG0055 events5 affected36 at risk EG0062 events2 affected37 at risk EG0073 events2 affected31 at risk EG0081 events1 affected32 at risk EG0090 events0 affected33 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected39 at risk EG0013 events3 affected39 at risk EG0021 events1 affected42 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0006 events5 affected39 at risk EG0013 events3 affected39 at risk EG0025 events4 affected42 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0012 events2 affected39 at risk EG0022 events1 affected42 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected39 at risk EG0014 events2 affected39 at risk EG0024 events1 affected42 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events2 affected39 at risk EG0012 events2 affected39 at risk EG0021 events1 affected42 at risk EG003
Headache	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0007 events4 affected39 at risk EG0012 events2 affected39 at risk EG0025 events3 affected42 at risk EG003
Dizziness	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0006 events5 affected39 at risk EG0011 events1 affected39 at risk EG0022 events2 affected42 at risk EG003
Lethargy	Nervous system disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0005 events3 affected39 at risk EG0012 events1 affected39 at risk EG0023 events2 affected42 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected39 at risk EG0011 events1 affected39 at risk EG0020 events0 affected42 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected39 at risk EG0020 events0 affected42 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0004 events4 affected39 at risk EG0011 events1 affected39 at risk EG0020 events0 affected42 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected39 at risk EG0020 events0 affected42 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected39 at risk EG0014 events4 affected39 at risk EG0020 events0 affected42 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0003 events3 affected39 at risk EG0014 events4 affected39 at risk EG0021 events1 affected42 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events2 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Influenza like illness	General disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0012 events2 affected39 at risk EG0020 events0 affected42 at risk EG003
Fatigue	General disorders	MedDRA (22.0)	Systematic Assessment	EG0003 events3 affected39 at risk EG0010 events0 affected39 at risk EG0022 events2 affected42 at risk EG003
Asthenia	General disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected39 at risk EG0021 events1 affected42 at risk EG003
Chest pain	General disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected39 at risk EG0024 events3 affected42 at risk EG003
Injection site bruising	General disorders	MedDRA (22.0)	Systematic Assessment	EG00011 events2 affected39 at risk EG0011 events1 affected39 at risk EG0022 events1 affected42 at risk EG003
Injection site erythema	General disorders	MedDRA (22.0)	Systematic Assessment	EG0004 events1 affected39 at risk EG0012 events2 affected39 at risk EG0024 events1 affected42 at risk EG003
Injection site haematoma	General disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events2 affected39 at risk EG0010 events0 affected39 at risk EG0025 events3 affected42 at risk EG003
Injection site haemorrhage	General disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected39 at risk EG0016 events1 affected39 at risk EG0023 events3 affected42 at risk EG003
Injection site pain	General disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0016 events2 affected39 at risk EG0022 events1 affected42 at risk EG003
Injection site reaction	General disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0012 events2 affected39 at risk EG0020 events0 affected42 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0021 events1 affected42 at risk EG003
Oedema peripheral	General disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected39 at risk EG0021 events1 affected42 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0007 events6 affected39 at risk EG0015 events4 affected39 at risk EG0025 events4 affected42 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0021 events1 affected42 at risk EG003
Bronchitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected39 at risk EG0020 events0 affected42 at risk EG003
Cystitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0022 events2 affected42 at risk EG003
Influenza	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0012 events2 affected39 at risk EG0021 events1 affected42 at risk EG003
Oral herpes	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Sinusitis	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0012 events2 affected39 at risk EG0020 events0 affected42 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0022 events2 affected42 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (22.0)	Systematic Assessment	EG0007 events4 affected39 at risk EG0016 events5 affected39 at risk EG0026 events5 affected42 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events2 affected39 at risk EG0011 events1 affected39 at risk EG0023 events3 affected42 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0021 events1 affected42 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected39 at risk EG0022 events2 affected42 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events2 affected39 at risk EG0010 events0 affected39 at risk EG0024 events4 affected42 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0012 events2 affected39 at risk EG0022 events2 affected42 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Hypertension	Vascular disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected39 at risk EG0020 events0 affected42 at risk EG003
Arrhythmia	Cardiac disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected39 at risk EG0012 events2 affected39 at risk EG0021 events1 affected42 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected39 at risk EG0010 events0 affected39 at risk EG0024 events4 affected42 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected39 at risk EG0020 events0 affected42 at risk EG003
Body temperature increased	Investigations	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0010 events0 affected39 at risk EG0020 events0 affected42 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events2 affected39 at risk EG0011 events1 affected39 at risk EG0020 events0 affected42 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (22.0)	Systematic Assessment	EG0000 events0 affected39 at risk EG0011 events1 affected39 at risk EG0020 events0 affected42 at risk EG003
Depression	Psychiatric disorders	MedDRA (22.0)	Systematic Assessment	EG0002 events2 affected39 at risk EG0010 events0 affected39 at risk EG0021 events1 affected42 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (22.0)	Systematic Assessment	EG0001 events1 affected39 at risk EG0011 events1 affected39 at risk EG0020 events0 affected42 at risk EG003

Title

Denominators

Categories

Title	Measurements
	OG0006.7± 5.1(5.1 to ) OG001-19.9± 5.1(5.1 to ) OG002-35.2± 5.1(5.1 to ) OG003-38.8± 4.9(4.9 to ) OG004-3.8± 4.7(4.7 to ) OG005-20.4± 4.6(4.6 to ) OG006-43.2± 4.3(4.3 to )

Group IDs	Statistical Method	P-Value	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Mixed Models Analysis	= 0.0003	Least Squares Mean Difference	-26.6	Standard Error of the Mean	7.2	2-Sided	95	-40.9	-12.4	Superiority
OG000 OG002	Mixed Models Analysis	< 0.0001	Least Squares Mean Difference	-42.0	Standard Error of the Mean	7.1	2-Sided	95	-56.1	-27.9	Superiority
OG000 OG003	Mixed Models Analysis	< 0.0001	Least Squares Mean Difference	-45.5	Standard Error of the Mean	7.1	2-Sided	95	-59.5	-31.5	Superiority
OG004 OG005	Mixed Models Analysis	= 0.0132	Least Squares Mean Difference	-16.6	Standard Error of the Mean	6.6	2-Sided	95	-29.7	-3.5	Superiority
OG004 OG006	Mixed Models Analysis	< 0.0001	Least Squares Mean Difference	-39.4	Standard Error of the Mean	6.4	2-Sided	95	-52.0	-26.8	Superiority

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 OG001		Mixed Models Analysis		= 0.0111		Least Squares Mean Difference	-21.8	Standard Error of the Mean	8.4	2-Sided	95	-38.4	-5.1					Superiority
OG000 OG002		Mixed Models Analysis		< 0.0001		Least Squares Mean Difference	-40.4	Standard Error of the Mean	8.2	2-Sided	95	-56.7	-24.0					Superiority

Title

Denominators

Categories

Title	Measurements
	OG0008.0± 5.4(5.4 to ) OG001-31.3± 5.4(5.4 to ) OG002-45.8± 5.3(5.3 to ) OG003-50.6± 5.2(5.2 to ) OG004-1.1± 5.8(5.8 to ) OG005-24.8± 5.7(5.7 to ) OG006-52.0± 5.3(5.3 to )

Group IDs	Statistical Method	P-Value	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Mixed Models Analysis	< 0.0001	Least Squares Mean Difference	-39.3	Standard Error of the Mean	7.6	2-Sided	95	-54.4	-24.3	Superiority
OG000 OG002	Mixed Models Analysis	< 0.0001	Least Squares Mean Difference	-53.8	Standard Error of the Mean	7.6	2-Sided	95	-68.8	-38.9	Superiority
OG000 OG003	Mixed Models Analysis	< 0.0001	Least Squares Mean Difference	-58.5	Standard Error of the Mean	7.5	2-Sided	95	-73.4	-43.7	Superiority
OG004 OG005	Mixed Models Analysis	= 0.0042	Least Squares Mean Difference	-23.7	Standard Error of the Mean	8.1	2-Sided	95	-39.7	-7.7	Superiority
OG004 OG006	Mixed Models Analysis	< 0.0001	Least Squares Mean Difference	-50.9	Standard Error of the Mean	7.8	2-Sided	95	-66.4	-35.4	Superiority

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 OG001		Mixed Models Analysis		= 0.0021		Least Squares Mean Difference	-30.6	Standard Error of the Mean	9.7	2-Sided	95	-49.8	-11.4					Superiority
OG000 OG002		Mixed Models Analysis		< 0.0001		Least Squares Mean Difference	-54.6	Standard Error of the Mean	9.5	2-Sided	95	-73.4	-35.8					Superiority

Group IDs	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Regression, Logistic	< 0.0001	Odds Ratio, log	19.4	2-Sided	95	5.1	72.8	Superiority
OG000 OG002	Regression, Logistic	< 0.0001	Odds Ratio, log	23.9	2-Sided	95	6.4	89.2	Superiority
OG000 OG003	Regression, Logistic	< 0.0001	Odds Ratio, log	22.1	2-Sided	95	6.0	80.5	Superiority
OG004 OG005	Regression, Logistic	= 0.0007	Odds Ratio, log	8.5	2-Sided	95	2.5	29.2	Superiority
OG004 OG006	Regression, Logistic	< 0.0001	Odds Ratio, log	42.3	2-Sided	95	10.4	172.3	Superiority

Group IDs	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Regression, Logistic	= 0.0100	Odds Ratio (OR)	9.6	2-Sided	95	1.7	53.5	Superiority
OG000 OG002	Regression, Logistic	= 0.0001	Odds Ratio (OR)	24.8	2-Sided	95	4.7	129.9	Superiority
OG000 OG003	Regression, Logistic	< 0.0001	Odds Ratio (OR)	36.1	2-Sided	95	6.7	194.7	Superiority
OG004 OG005	Regression, Logistic	= 0.3185	Odds Ratio (OR)	2.0	2-Sided	95	0.5	8.2	Superiority
OG004 OG006	Regression, Logistic	< 0.0001	Odds Ratio (OR)	14.5	2-Sided	95	3.9	54.2	Superiority

Group IDs	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Regression, Logistic	= 0.0718	Odds Ratio (OR)	4.8	2-Sided	95	0.9	26.5	Superiority
OG000 OG002	Regression, Logistic	= 0.0048	Odds Ratio (OR)	11.4	2-Sided	95	2.1	62.1	Superiority
OG000 OG003	Regression, Logistic	= 0.0015	Odds Ratio (OR)	14.7	2-Sided	95	2.8	76.8	Superiority
OG004 OG005	Regression, Logistic	= 0.5270	Odds Ratio (OR)	1.7	2-Sided	95	0.3	8.4	Superiority
OG004 OG006	Regression, Logistic	= 0.0047	Odds Ratio (OR)	7.7	2-Sided	95	1.9	31.7	Superiority

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 OG001		Mixed Models Analysis		= 0.0059		Least Squares Mean Difference	-32.5	Standard Error of the Mean	11.5	2-Sided	95	-55.5	-9.6					Superiority
OG000 OG002		Mixed Models Analysis		< 0.0001		Least Squares Mean Difference	-54.5	Standard Error of the Mean	11.3	2-Sided	95	-77.0	-32.0					Superiority

Title

Denominators

Categories

Title	Measurements
	OG0006.1± 4.0(4.0 to ) OG001-31.0± 4.0(4.0 to ) OG002-40.3± 4.0(4.0 to ) OG003-45.4± 3.9(3.9 to ) OG004-0.4± 4.5(4.5 to ) OG005-22.6± 4.4(4.4 to ) OG006-46.8± 4.1(4.1 to )

Group IDs	Statistical Method	P-Value	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Mixed Models Analysis	< .0001	Least Squares Mean Difference	-37.1	Standard Error of the Mean	5.7	2-Sided	95	-48.4	-25.8	Superiority
OG000 OG002	Mixed Models Analysis	< .0001	Least Squares Mean Difference	-46.4	Standard Error of the Mean	5.6	2-Sided	95	-57.5	-35.2	Superiority
OG000 OG003	Mixed Models Analysis	< .0001	Least Squares Mean Difference	-51.5	Standard Error of the Mean	5.6	2-Sided	95	-62.5	-40.4	Superiority
OG004 OG005	Mixed Models Analysis	= 0.0006	Least Squares Mean Difference	-22.2	Standard Error of the Mean	6.2	2-Sided	95	-34.6	-9.8	Superiority
OG004 OG006	Mixed Models Analysis	< .0001	Least Squares Mean Difference	-46.4	Standard Error of the Mean	6.1	2-Sided	95	-58.4	-34.4	Superiority

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 OG001		Mixed Models Analysis		= 0.0001		Least Squares Mean Difference	-28.4	Standard Error of the Mean	7.1	2-Sided	95	-42.6	-14.3					Superiority
OG000 OG002		Mixed Models Analysis		< .0001		Least Squares Mean Difference	-49.3	Standard Error of the Mean	7.0	2-Sided	95	-63.2	-35.4					Superiority

Title

Denominators

Categories

Title	Measurements
	OG0008.1± 4.5(4.5 to ) OG001-38.0± 4.2(4.2 to ) OG002-47.7± 4.0(4.0 to ) OG003-53.4± 3.9(3.9 to ) OG004-6.9± 4.7(4.7 to ) OG005-32.1± 4.5(4.5 to ) OG006-52.8± 4.1(4.1 to )

Group IDs	Statistical Method	P-Value	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Regression, Linear	< .0001	Adjusted Mean Difference	-46.1	Standard Error of the Mean	6.0	2-Sided	95	-57.8	-34.3	Superiority
OG000 OG002	Regression, Linear	< .0001	Adjusted Mean Difference	-55.8	Standard Error of the Mean	5.9	2-Sided	95	-67.3	-44.3	Superiority
OG000 OG003	Regression, Linear	< .0001	Adjusted Mean Difference	-61.5	Standard Error of the Mean	5.8	2-Sided	95	-72.9	-50.0	Superiority
OG004 OG005	Regression, Linear	= 0.0001	Adjusted Mean Difference	-25.2	Standard Error of the Mean	6.5	2-Sided	95	-38.0	-12.4	Superiority
OG004 OG006	Regression, Linear	< .0001	Adjusted Mean Difference	-45.9	Standard Error of the Mean	6.3	2-Sided	95	-58.4	-33.5	Superiority

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 OG001		Regression, Linear		= 0.0228		Adjusted Mean Difference	-17.1	Standard Error of the Mean	7.5	2-Sided	95	-31.8	-2.4					Superiority
OG000 OG002		Regression, Linear		< .0001		Adjusted Mean Difference	-45.3	Standard Error of the Mean	7.3	2-Sided	95	-59.6	-31.0					Superiority

Title

Denominators

Categories

Title	Measurements
	OG0000.3± 3.9(3.9 to ) OG001-10.3± 4.1(4.1 to ) OG002-11.6± 4.0(4.0 to ) OG003-8.9± 4.0(4.0 to ) OG0040.8± 3.7(3.7 to ) OG005-15.7± 3.7(3.7 to ) OG006-15.7± 3.3(3.3 to )

Group IDs	Statistical Method	P-Value	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Regression, Linear	= 0.0635	Adjusted Mean Difference	-10.6	Standard Error of the Mean	5.7	2-Sided	95	-21.8	0.6	Superiority
OG000 OG002	Regression, Linear	= 0.0314	Adjusted Mean Difference	-11.9	Standard Error of the Mean	5.5	2-Sided	95	-22.8	-1.1	Superiority
OG000 OG003	Regression, Linear	= 0.0923	Adjusted Mean Difference	-9.2	Standard Error of the Mean	5.5	2-Sided	95	-19.9	1.5	Superiority
OG004 OG005	Regression, Linear	= 0.0017	Adjusted Mean Difference	-16.5	Standard Error of the Mean	5.3	2-Sided	95	-26.8	-6.2	Superiority
OG004 OG006	Regression, Linear	= 0.0009	Adjusted Mean Difference	-16.5	Standard Error of the Mean	4.9	2-Sided	95	-26.2	-6.8	Superiority

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 OG001		Regression, Linear		= 0.0054		Adjusted Mean Difference	-16.1	Standard Error of the Mean	5.8	2-Sided	95	-27.4	-4.7					Superiority
OG000 OG002		Regression, Linear		= 0.0085		Adjusted Mean Difference	-14.6	Standard Error of the Mean	5.5	2-Sided	95	-25.4	-3.7					Superiority

ID	Term
D006949	Hyperlipidemias
D050171	Dyslipidemias
D052439	Lipid Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases