Efficacy and Safety of Inclisiran as Monotherapy in Patie... | NCT05763875

Efficacy and Safety of Inclisiran as Monotherapy in Patie... | NCT05763875 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Inclisiran	Experimental	Inclisiran s.c and Placebo p.o	Drug: Inclisiran Drug: Matching Placebo for Ezetimibe
Ezetimibe	Active Comparator	Placebo s.c. and Ezetimibe p.o.	Drug: Ezetimibe Drug: Matching Placebo for Inclisiran
Placebo	Placebo Comparator	Placebo s.c. and Placebo p.o.	Drug: Matching Placebo for Inclisiran Drug: Matching Placebo for Ezetimibe

Name	Type	Description	Arm Group Labels	Other Names
Inclisiran	Drug	284 mg (equivalent to 300 mg inclisiran sodium) subcutaneous injection given on Day 1 and Day 90	Inclisiran

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 150	Percentage change in LDL-C from Baseline (day 1) to Day 150, Inclisiran arm versus Ezetimibe and placebo. There were two estimands of interest in comparing efficacy of inclisiran as monotherapy against that of placebo or ezetimibe that differ on the treatment of interest used for each and the management of intercurrent events as follows: Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen. Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.	Baseline, Day 150

Secondary Outcomes

Measure	Description	Time Frame
Absolute Change in LDL-C From Baseline to Day 150	Absolute change in LDL-C from Baseline (Day 1) to Day 150, Inclisiran arm versus Ezetimibe and placebo. There were two estimands of interest in comparing efficacy of inclisiran as monotherapy against that of placebo or ezetimibe that differ on the treatment of interest used for each and the management of intercurrent events as follows: Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen. Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.

Contacts/Locations Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Parkway Medical Center		Birmingham	Alabama	35215	United States
SEC Clinical Research

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
40392667	Derived	Taub PR, Gutierrez A, Wewers D, Garcia Cantu E, Cao H, Deck C, Lesogor A, Ott D, Mena-Madrazo J, Zang X, Wright RS. Safety and Lipid-Lowering Efficacy of Inclisiran Monotherapy in Patients Without ASCVD: The VICTORION-Mono Randomized Clinical Trial. J Am Coll Cardiol. 2025 Jul 22;86(3):196-208. doi: 10.1016/j.jacc.2025.04.049. Epub 2025 May 5.

Label	URL
A Plain Language Trial Summary is available on www.novctrd.com	View source

Results Section

Participant Flow Module

ID	Title	Description
FG000	Inclisiran	Inclisiran s.c and Placebo p.o
FG001	Ezetimibe	Placebo s.c. and Ezetimibe p.o.

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	Feb 8, 2023	Jun 17, 2025

Arm/Group Information

ID	Title	Description
BG000	Inclisiran	Inclisiran s.c and Placebo p.o
BG001	Ezetimibe	Placebo s.c. and Ezetimibe p.o.
BG002	Placebo	Placebo s.c. and Placebo p.o.
BG003	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, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020 BG003

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00045.7± 11.74 BG00146.3± 10.90 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000104 BG00156 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG00010 BG00110 BG002

Baseline Low-Density Lipoprotein Cholesterol (LDL-C)

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG000135.8± 27.01 BG001134.4± 25.82 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

Percentage Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 150

Percentage change in LDL-C from Baseline (day 1) to Day 150, Inclisiran arm versus Ezetimibe and placebo.

There were two estimands of interest in comparing efficacy of inclisiran as monotherapy against that of placebo or ezetimibe that differ on the treatment of interest used for each and the management of intercurrent events as follows:

Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen.
Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.

Full Analysis Set, all randomized participants.

Posted

Least Squares Mean

95% Confidence Interval

Percentage change from baseline

Baseline, Day 150

ID	Title	Description
OG000	Inclisiran	Inclisiran s.c and Placebo p.o
OG001	Ezetimibe	Placebo s.c. and Ezetimibe p.o.
OG002	Placebo	Placebo s.c. and Placebo p.o.

Units	Counts
Participants	OG000174 OG00189 OG00287

Title

Denominators

Categories

LS Mean (Treatment Policy estimand)

Title	Measurements
	OG000-46.54(-50.20 to -42.88) OG001-11.17(-15.34 to -7.00) OG0021.37(-3.07 to 5.80)

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	Treatment Policy Estimand	ANCOVA		<0.0001		LS Mean Difference	-35.37			2-Sided	95	-40.88	-29.86					Superiority
OG000 OG002	Treatment Policy Estimand	ANCOVA

Secondary

Absolute Change in LDL-C From Baseline to Day 150

Absolute change in LDL-C from Baseline (Day 1) to Day 150, Inclisiran arm versus Ezetimibe and placebo.

Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen.
Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.

Full Analysis Set, all randomized participants.

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

Baseline, Day 150

ID	Title	Description
OG000	Inclisiran	Inclisiran s.c and Placebo p.o
OG001	Ezetimibe	Placebo s.c. and Ezetimibe p.o.
OG002	Placebo

Secondary

Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 150

Percentage change in PCSK9 from Baseline (Day 1) to Day 150 , Inclisiran arm versus Ezetimibe and placebo.

Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen.
Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.

Full Analysis Set, all randomized participants with a valid assessment for the outcome measure.

Posted

Least Squares Mean

95% Confidence Interval

Percentage change from baseline

Baseline, Day 150

ID	Title	Description
OG000	Inclisiran	Inclisiran s.c and Placebo p.o
OG001	Ezetimibe	Placebo s.c. and Ezetimibe p.o.

Secondary

Percentage Change in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Day 150

Percentage change in non-HDL-C from Baseline (Day 1) to Day 150, Inclisiran arm versus Ezetimibe and placebo.

Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen.
Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.

Full Analysis Set, all randomized participants.

Posted

Least Squares Mean

95% Confidence Interval

Percentage change from baseline

Baseline, Day 150

ID	Title	Description
OG000	Inclisiran	Inclisiran s.c and Placebo p.o
OG001	Ezetimibe	Placebo s.c. and Ezetimibe p.o.

Secondary

Percentage Change in Total Cholesterol (TC)/HDL-C Ratio From Baseline to Day 150

Percentage change in total cholesterol/HDL-C ratio from Baseline (Day1) to Day 150, Inclisiran arm versus Ezetimibe and placebo.

Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen.
Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strate

Full Analysis Set, all randomized participants.

Posted

Least Squares Mean

95% Confidence Interval

Percentage change from baseline

Baseline, Day 150

ID	Title	Description
OG000	Inclisiran	Inclisiran s.c and Placebo p.o
OG001	Ezetimibe	Placebo s.c. and Ezetimibe p.o.

Secondary

Percentage Change in Apolipoprotein B (Apo B) From Baseline to Day 150

Percentage change in Apo B from Baseline (Day 1) to Day 150, Inclisiran arm versus Ezetimibe and placebo.

Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen.
Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.

Full Analysis Set, all randomized participants.

Posted

Least Squares Mean

95% Confidence Interval

Percentage change from baseline

Baseline, Day 150

ID	Title	Description
OG000	Inclisiran	Inclisiran s.c and Placebo p.o
OG001	Ezetimibe	Placebo s.c. and Ezetimibe p.o.
OG002

Secondary

Percentage Change in Apo B/Apo A-1 Ratio From Baseline to Day 150

Percentage change in Apo B/Apo A-1 ratio from baseline (Day 1) to Day 150, Inclisiran arm versus Ezetimibe and placebo.

Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen.
Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.

Full Analysis Set, all randomized participants.

Posted

Least Squares Mean

95% Confidence Interval

Percentage change from baseline

Baseline, Day 150

ID	Title	Description
OG000	Inclisiran	Inclisiran s.c and Placebo p.o
OG001	Ezetimibe	Placebo s.c. and Ezetimibe p.o.
OG002

Secondary

Change in Lipoprotein (a) [Lp(a)] From Baseline to Day 150

Day 150 / Baseline ratio in Lp(a) in Inclisiran arm versus Ezetimibe and placebo.

Monotherapy Estimand: Inclisiran as monotherapy compared to the use of comparator. This estimand uses a hypothetical strategy where participants who permanently discontinued treatment, died or used other LLTs were handled in a hypothetical scenario of what would have happened if the intercurrent event did not happen.
Treatment-policy Estimand: Inclisiran as monotherapy compared to the use of comparator with or without other lipid lowering therapies (LLTs) added. This estimand ignored the use of other LLTs and treatment discontinuation. Deaths (if any) were handled as an unfavorable outcome using a composite variable strategy.

Full Analysis Set, all randomized participants with a valid assessment for the outcome measure.

Posted

Geometric Least Squares Mean

95% Confidence Interval

Ratio from baseline

Baseline, Day 150

ID	Title	Description
OG000	Inclisiran	Inclisiran s.c and Placebo p.o
OG001	Ezetimibe	Placebo s.c. and Ezetimibe p.o.
OG002

Secondary

Incidence of Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)

Incidence of TEAEs (regardless of seriousness) and SAEs by treatment group, including changes in laboratory results qualifying and reported as AEs.

Safety Analysis Set, all participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

From first dose of study treatment on Day 1 up to Day 180

ID	Title	Description
OG000	Inclisiran	Inclisiran s.c and Placebo p.o
OG001	Ezetimibe	Placebo s.c. and Ezetimibe p.o.
OG002	Placebo	Placebo s.c. and Placebo p.o.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Inclisiran	Inclisiran s.c and Placebo p.o	174	1	174	19	174
EG001	Ezetimibe	Placebo s.c. and Ezetimibe p.o.	89	0	89	18	89
EG002	Placebo	Placebo s.c. and Placebo p.o.	87	0	87	13	87
EG003	Total	Total	350	1	350	50	350

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Femur fracture	Injury, poisoning and procedural complications	MedDRA (27.0)	Systematic Assessment		EG0001 affected174 at risk EG0010 affected89 at risk EG0020 affected87 at risk EG0031 affected350 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (27.0)	Systematic Assessment	EG0002 affected174 at risk EG0011 affected89 at risk EG0022 affected87 at risk EG0035 affected350 at risk
Vomiting	Gastrointestinal disorders	MedDRA (27.0)	Systematic Assessment	EG0002 affected174 at risk EG0012 affected89 at risk EG0020 affected87 at risk EG003
COVID-19	Infections and infestations	MedDRA (27.0)	Systematic Assessment	EG0001 affected174 at risk EG0012 affected89 at risk EG0023 affected87 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (27.0)	Systematic Assessment	EG0002 affected174 at risk EG0012 affected89 at risk EG0020 affected87 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (27.0)	Systematic Assessment	EG0006 affected174 at risk EG0013 affected89 at risk EG0023 affected87 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (27.0)	Systematic Assessment	EG0002 affected174 at risk EG0012 affected89 at risk EG0021 affected87 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (27.0)	Systematic Assessment	EG0003 affected174 at risk EG0012 affected89 at risk EG0022 affected87 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (27.0)	Systematic Assessment	EG0000 affected174 at risk EG0012 affected89 at risk EG0021 affected87 at risk EG003
Blood pressure increased	Investigations	MedDRA (27.0)	Systematic Assessment	EG0001 affected174 at risk EG0012 affected89 at risk EG0020 affected87 at risk EG003
Headache	Nervous system disorders	MedDRA (27.0)	Systematic Assessment	EG0006 affected174 at risk EG0010 affected89 at risk EG0020 affected87 at risk EG003
Hypertonic bladder	Renal and urinary disorders	MedDRA (27.0)	Systematic Assessment	EG0000 affected174 at risk EG0012 affected89 at risk EG0020 affected87 at risk EG003
Hypertension	Vascular disorders	MedDRA (27.0)	Systematic Assessment	EG0001 affected174 at risk EG0011 affected89 at risk EG0022 affected87 at risk EG003

Title

Denominators

Categories

LS Mean (Treatment Policy estimand)

Title	Measurements
	OG000-64.86(-69.27 to -60.46) OG001-17.55(-22.53 to -12.57) OG002-1.29(-6.40 to 3.82)

LS Mean (Monotherapy estimand)

Title	Measurements
	OG000-68.57(-72.59 to -64.56) OG001-18.52(-23.16 to -13.89) OG002-1.07(-6.32 to 4.19)

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Treatment Policy Estimand	ANCOVA	<0.0001	LS Mean Difference	-47.37	2-Sided	95	-53.91	-40.72	Superiority
OG000 OG002	Treatment Policy Estimand	ANCOVA	<0.0001	LS Mean Difference	-63.57	2-Sided	95	-70.28	-56.87	Superiority
OG000 OG001	Monotherapy Estimand	ANCOVA	<0.0001	LS Mean Difference	-50.05	2-Sided	95	-56.16	-43.94	Superiority
OG000 OG002	Monotherapy Estimand	ANCOVA	<0.0001	LS Mean Difference	-67.51	2-Sided	95	-74.09	-60.92	Superiority

Title

Denominators

Categories

LS Mean (Treatment Policy estimand)

- ParticipantsOG000172
- ParticipantsOG00189
- ParticipantsOG00285

Title	Measurements
	OG000-67.12(-73.21 to -61.03) OG0016.04(-0.10 to 12.18) OG0027.82(0.35 to 15.29)

LS Mean (Monotherapy estimand)

- ParticipantsOG000172
- ParticipantsOG00189
- ParticipantsOG00285

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Treatment Policy Estimand	ANCOVA	<0.0001	LS Mean Difference	-73.16	2-Sided	95	-81.76	-64.56	Superiority
OG000 OG002	Treatment Policy Estimand	ANCOVA	<0.0001	LS Mean Difference	-74.94	2-Sided	95	-84.51	-65.37	Superiority
OG000 OG001	Monotherapy Estimand	ANCOVA	<0.0001	LS Mean Difference	-76.87	2-Sided	95	-85.12	-68.62	Superiority
OG000 OG002	Monotherapy Estimand	ANCOVA	<0.0001	LS Mean Difference	-79.47	2-Sided	95	-88.77	-70.17	Superiority

Title

Denominators

Categories

LS Mean (Treatment Policy estimand)

Title	Measurements
	OG000-40.45(-43.50 to -37.40) OG001-9.97(-13.34 to -6.61) OG0021.88(-2.75 to 6.50)

LS Mean (Monotherapy estimand)

Title	Measurements
	OG000-42.82(-45.62 to -40.02) OG001-10.84(-13.84 to -7.84) OG0022.04(-2.63 to 6.71)

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Treatment Policy Estimand	ANCOVA	<0.0001	LS Mean Difference	-30.48	2-Sided	95	-34.98	-25.98	Superiority
OG000 OG002	Treatment Policy Estimand	ANCOVA	<0.0001	LS Mean Difference	-42.32	2-Sided	95	-47.83	-36.82	Superiority
OG000 OG001	Monotherapy Estimand	ANCOVA	<0.0001	LS Mean Difference	-31.98	2-Sided	95	-36.07	-27.89	Superiority
OG000 OG002	Monotherapy Estimand	ANCOVA	<0.0001	LS Mean Difference	-44.86	2-Sided	95	-50.28	-39.44	Superiority

Title

Denominators

Categories

LS Mean (Treatment Policy estimand)

Title	Measurements
	OG000-31.54(-35.43 to -27.65) OG001-6.70(-10.61 to -2.78) OG0022.31(-4.05 to 8.68)

LS Mean (Monotherapy estimand)

Title	Measurements
	OG000-33.56(-37.32 to -29.79) OG001-6.98(-10.99 to -2.97) OG0022.51(-3.90 to 8.91)

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Treatment Policy Estimand	ANCOVA	<0.0001	LS Mean Difference	-24.84	2-Sided	95	-30.32	-19.36	Superiority
OG000 OG002	Treatment Policy Estimand	ANCOVA	<0.0001	LS Mean Difference	-33.85	2-Sided	95	-41.27	-26.44	Superiority
OG000 OG001	Monotherapy Estimand	ANCOVA	<0.0001	LS Mean Difference	-26.58	2-Sided	95	-32.07	-21.09	Superiority
OG000 OG002	Monotherapy Estimand	ANCOVA	<0.0001	LS Mean Difference	-36.06	2-Sided	95	-43.46	-28.67	Superiority

Title

Denominators

Categories

LS Mean (Treatment Policy estimand)

Title	Measurements
	OG000-37.39(-40.25 to -34.54) OG001-8.41(-11.71 to -5.12) OG002-0.73(-4.18 to 2.72)

LS Mean (Monotherapy estimand)

Title	Measurements
	OG000-39.36(-42.00 to -36.72) OG001-9.20(-12.13 to -6.28) OG002-0.58(-4.07 to 2.90)

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Treatment Policy Estimand	ANCOVA	<0.0001	LS Mean Difference	-28.98	2-Sided	95	-33.30	-24.65	Superiority
OG000 OG002	Treatment Policy Estimand	ANCOVA	<0.0001	LS Mean Difference	-36.66	2-Sided	95	-41.10	-32.22	Superiority
OG000 OG001	Monotherapy Estimand	ANCOVA	<0.0001	LS Mean Difference	-30.16	2-Sided	95	-34.08	-26.23	Superiority
OG000 OG002	Monotherapy Estimand	ANCOVA	<0.0001	LS Mean Difference	-38.78	2-Sided	95	-43.12	-34.43	Superiority

Title

Denominators

Categories

LS Mean (Treatment Policy estimand)

Title	Measurements
	OG000-37.79(-43.03 to -32.55) OG001-7.55(-11.74 to -3.36) OG002-2.65(-5.69 to 0.39)

LS Mean (Monotherapy estimand)

Title	Measurements
	OG000-40.03(-45.25 to -34.82) OG001-7.69(-12.00 to -3.37) OG002-2.65(-5.81 to 0.50)

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Treatment Policy Estimand	ANCOVA	<0.0001	LS Mean Difference	-30.24	2-Sided	95	-36.92	-23.57	Superiority
OG000 OG002	Treatment Policy Estimand	ANCOVA	<0.0001	LS Mean Difference	-35.15	2-Sided	95	-41.18	-29.12	Superiority
OG000 OG001	Monotherapy Estimand	ANCOVA	<0.0001	LS Mean Difference	-32.34	2-Sided	95	-39.10	-25.59	Superiority
OG000 OG002	Monotherapy Estimand	ANCOVA	<0.0001	LS Mean Difference	-37.38	2-Sided	95	-43.44	-31.31	Superiority

Title

Denominators

Categories

LS Mean (Treatment Policy estimand)

Title	Measurements
	OG0000.690(0.611 to 0.780) OG0010.911(0.830 to 1.000) OG0020.923(0.803 to 1.060)

LS Mean (Monotherapy estimand)

Title	Measurements
	OG0000.687(0.612 to 0.722) OG0010.912(0.836 to 0.95) OG0020.922(0.800 to 1.062)

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Treatment Policy Estimand	ANCOVA	0.0002	Ratio of Geometric Mean	0.757	2-Sided	95	0.650	0.882	Superiority
OG000 OG002	Treatment Policy Estimand	ANCOVA	0.0010	Ratio of Geometric Mean	0.748	2-Sided	95	0.622	0.898	Superiority
OG000 OG001	Monotherapy Estimand	ANCOVA	<0.0001	Ratio of Geometric Mean	0.753	2-Sided	95	0.652	0.871	Superiority
OG000 OG002	Monotherapy Estimand	ANCOVA	0.0008	Ratio of Geometric Mean	0.746	2-Sided	95	0.622	0.893	Superiority

Title

Denominators

Categories

AEs

Title	Measurements
	OG00054 OG00127 OG00225

AEs related to s.c. treatment (Inclisiran or s.c. matching placebo)

Title	Measurements
	OG00011 OG0014 OG0020

AEs related to p.o. treatment (ezetimibe or p.o. matching placebo)

Title	Measurements
	OG0003 OG0012 OG0022

SAEs

Title	Measurements
	OG0001 OG0010 OG0020

SAEs related to s.c. treatment (Inclisiran or s.c. matching placebo)

Title	Measurements
	OG0000 OG0010 OG0020

SAEs related to p.o. treatment (ezetimibe or p.o. matching placebo)

Title	Measurements
	OG0000 OG0010 OG0020

Fatal SAEs

Title	Measurements
	OG0000 OG0010 OG0020

AEs leading to treatment discontinuation of inclisiran or s.c. matching placebo

Title	Measurements
	OG0003 OG0010 OG0020

AEs leading to treatment discontinuation of ezetimibe or p.o. matching placebo

Title	Measurements
	OG0004 OG0010 OG0020

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

ID	Term
D001384	Azetidines
D001385	Azetines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds