Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol (ORION-11)

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ClinicalTrials.gov Identifier: NCT03400800

Recruitment Status : Completed

First Posted : January 17, 2018

Results First Posted : August 21, 2020

Last Update Posted : August 21, 2020

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Sponsor:

Information provided by (Responsible Party):

The Medicines Company

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Treatment
Conditions	ASCVD Risk Factor, Cardiovascular Elevated Cholesterol
Interventions	Drug: Inclisiran Sodium Drug: Placebo
Enrollment	1617

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Inclisiran	Placebo
Arm/Group Description	Inclisiran sodium 300 milligrams (m...	Placebo (1.5 mL) will be administer...
Arm/Group Description	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) in 1.5 milliliters (mL) will be administered as a SC injection on Day 1, Day 90, and then every 6 months Inclisiran Sodium: Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.	Placebo (1.5 mL) will be administered as a SC injection of saline solution on Day 1, Day 90, and then every 6 months Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).
Period Title: Overall Study
Started	810	807
Completed	772	770
Not Completed	38	37

Baseline Characteristics

Arm/Group Title		Inclisiran	Placebo	Total
Arm/Group Description		Inclisiran sodium 300 milligrams (m...	Placebo (1.5 mL) will be administer...	Total of all reporting groups
Arm/Group Description		Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) in 1.5 milliliters (mL) will be administered as a SC injection on Day 1, Day 90, and then every 6 months Inclisiran Sodium: Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.	Placebo (1.5 mL) will be administered as a SC injection of saline solution on Day 1, Day 90, and then every 6 months Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).	Total of all reporting groups
Overall Number of Baseline Participants		810	807	1617
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	810 participants	807 participants	1617 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	367 45.3%	366 45.4%	733 45.3%
	>=65 years	443 54.7%	441 54.6%	884 54.7%
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	810 participants	807 participants	1617 participants
		64.8 (8.29)	64.8 (8.68)	64.8 (8.48)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	810 participants	807 participants	1617 participants
	Female	231 28.5%	226 28.0%	457 28.3%
	Male	579 71.5%	581 72.0%	1160 71.7%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	810 participants	807 participants	1617 participants
	American Indian or Alaska Native	1 0.1%	0 0.0%	1 0.1%
	Asian	6 0.7%	2 0.2%	8 0.5%
	Native Hawaiian or Other Pacific Islander	0 0.0%	1 0.1%	1 0.1%
	Black or African American	12 1.5%	8 1.0%	20 1.2%
	White	791 97.7%	796 98.6%	1587 98.1%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	810 participants	807 participants	1617 participants
Hungary		52	52	104
Czechia		10	11	21
Ukraine		55	54	109
Poland		360	357	717
South Africa		60	61	121
United Kingdom		231	231	462
Germany		42	41	83

Outcome Measures

1.Primary Outcome


Title	Percentage Change in LDL-C From Baseline to Day 510
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline, Day 510

Outcome Measure Data

Analysis Population Description

ITT population


Arm/Group Title	Inclisiran	Placebo
Arm/Group Description:	Inclisiran sodium 300 milligrams (m...	Placebo (1.5 mL) administered as a ...
Arm/Group Description:	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) in 1.5 millilitres (mL) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo (1.5 mL) administered as a subcutaneous injection of sterile saline solution (0.9% sodium chloride in water for injection) on Day 1, Day 90, and then every 6 months.
Overall Number of Participants Analyzed	810	807
Least Squares Mean (95% Confidence Interval) Unit of Measure: Percent change
	-49.3 (-51.22 to -47.48)	4.2 (1.62 to 6.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	The a priori threshold for statistical significance was <0.05
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-53.5
	Confidence Interval	(2-Sided) 95% -56.66 to -50.35
	Estimation Comments	Represents the least squares means difference from Placebo

2.Primary Outcome


Title	Time-adjusted Percent Change in LDL-C Levels From Baseline After Day 90 and up to Day 540
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline, Day 90 to Day 540

Outcome Measure Data

Analysis Population Description

ITT population


Arm/Group Title	Inclisiran	Placebo
Arm/Group Description:	Inclisiran sodium 300 milligrams (m...	Placebo (1.5 mL) administered as a ...
Arm/Group Description:	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) in 1.5 millilitres (mL) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo (1.5 mL) administered as a subcutaneous injection of sterile saline solution (0.9% sodium chloride in water for injection) on Day 1, Day 90, and then every 6 months.
Overall Number of Participants Analyzed	810	807
Least Squares Mean (95% Confidence Interval) Unit of Measure: Percent change
	-45.82 (-47.52 to -44.13)	3.35 (1.65 to 5.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	The a priori threshold for statistical significance was <0.05
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-49.17
	Confidence Interval	(2-Sided) 95% -51.57 to -46.77
	Estimation Comments	Represents the least squares means difference from Placebo

3.Secondary Outcome


Title	Absolute Change In LDL-C From Baseline To Day 510
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline, Day 510

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Inclisiran	Placebo
Arm/Group Description:	Inclisiran sodium 300 milligrams (m...	Placebo (1.5 mL) administered as a ...
Arm/Group Description:	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) in 1.5 millilitres (mL) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo (1.5 mL) administered as a subcutaneous injection of sterile saline solution (0.9% sodium chloride in water for injection) on Day 1, Day 90, and then every 6 months.
Overall Number of Participants Analyzed	810	807
Least Squares Mean (95% Confidence Interval) Unit of Measure: mg/dL
	-50.91 (-53.14 to -48.67)	0.96 (-1.26 to 3.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<.0001
	Comments	The a priori threshold for statistical significance was <0.05
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-51.87
	Confidence Interval	(2-Sided) 95% -55.01 to -48.72
	Estimation Comments	Represents the least squares means difference from Placebo

4.Secondary Outcome


Title	Time-adjusted Absolute Change in LDL-C From Baseline After Day 90 and up to Day 540
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline, Day 90 to Day 540

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Inclisiran	Placebo
Arm/Group Description:	Inclisiran sodium 300 milligrams (m...	Placebo (1.5 mL) administered as a ...
Arm/Group Description:	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) in 1.5 millilitres (mL) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo (1.5 mL) administered as a subcutaneous injection of sterile saline solution (0.9% sodium chloride in water for injection) on Day 1, Day 90, and then every 6 months.
Overall Number of Participants Analyzed	810	807
Least Squares Mean (95% Confidence Interval) Unit of Measure: mg/dL
	-48.63 (-50.37 to -46.89)	0.31 (-1.42 to 2.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	The a priori threshold for statistical significance was <0.05
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-48.94
	Confidence Interval	(2-Sided) 95% -51.39 to -46.48
	Estimation Comments	Represents the least squares means difference from Placebo

5.Secondary Outcome


Title	Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 510
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline, Day 510

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Inclisiran	Placebo
Arm/Group Description:	Inclisiran sodium 300 milligrams (m...	Placebo (1.5 mL) administered as a ...
Arm/Group Description:	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) in 1.5 millilitres (mL) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo (1.5 mL) administered as a subcutaneous injection of sterile saline solution (0.9% sodium chloride in water for injection) on Day 1, Day 90, and then every 6 months.
Overall Number of Participants Analyzed	810	807
Least Squares Mean (95% Confidence Interval) Unit of Measure: Percent change
	-63.64 (-65.55 to -61.74)	15.62 (13.72 to 17.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	The a priori threshold for statistical significance was <0.05
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-79.27
	Confidence Interval	(2-Sided) 95% -81.97 to -76.57
	Estimation Comments	Represents the least squares means difference from Placebo

6.Secondary Outcome


Title	Percentage Change in Total Cholesterol From Baseline to Day 510
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline, Day 510

Outcome Measure Data

Analysis Population Description

ITT Population


Arm/Group Title	Inclisiran	Placebo
Arm/Group Description:	Inclisiran sodium 300 milligrams (m...	Placebo (1.5 mL) administered as a ...
Arm/Group Description:	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) in 1.5 millilitres (mL) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo (1.5 mL) administered as a subcutaneous injection of sterile saline solution (0.9% sodium chloride in water for injection) on Day 1, Day 90, and then every 6 months.
Overall Number of Participants Analyzed	810	807
Least Squares Mean (95% Confidence Interval) Unit of Measure: Percent change
	-28.00 (-29.40 to -26.60)	1.79 (0.38 to 3.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	The a priori threshold for statistical significance was <0.05
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-29.79
	Confidence Interval	(2-Sided) 95% -31.78 to -27.81
	Estimation Comments	Represents the least squares means difference from Placebo

7.Secondary Outcome


Title	Percentage Change in Apolipoprotein B (ApoB) From Baseline to Day 510
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline, Day 510

Outcome Measure Data

Analysis Population Description

ITT Population


Arm/Group Title	Inclisiran	Placebo
Arm/Group Description:	Inclisiran sodium 300 milligrams (m...	Placebo (1.5 mL) administered as a ...
Arm/Group Description:	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) in 1.5 millilitres (mL) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo (1.5 mL) administered as a subcutaneous injection of sterile saline solution (0.9% sodium chloride in water for injection) on Day 1, Day 90, and then every 6 months.
Overall Number of Participants Analyzed	810	807
Least Squares Mean (95% Confidence Interval) Unit of Measure: Percent change
	-38.15 (-39.76 to -36.54)	0.79 (-0.82 to 2.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	The a priori threshold for statistical significance was <0.05
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-38.94
	Confidence Interval	(2-Sided) 95% -41.21 to -36.67
	Estimation Comments	Represents the least squares means difference from Placebo

8.Secondary Outcome


Title	Percentage Change in Non-HDL-C From Baseline to Day 510
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline, Day 510

Outcome Measure Data

Analysis Population Description

ITT Population


Arm/Group Title	Inclisiran	Placebo
Arm/Group Description:	Inclisiran sodium 300 milligrams (m...	Placebo (1.5 mL) administered as a ...
Arm/Group Description:	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) in 1.5 millilitres (mL) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo (1.5 mL) administered as a subcutaneous injection of sterile saline solution (0.9% sodium chloride in water for injection) on Day 1, Day 90, and then every 6 months.
Overall Number of Participants Analyzed	810	807
Least Squares Mean (95% Confidence Interval) Unit of Measure: Percent change
	-41.16 (-43.09 to -39.24)	2.15 (0.22 to 4.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	The a priori threshold for statistical significance was <0.05
	Method	ANCOVA
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-43.32
	Confidence Interval	(2-Sided) 95% -46.04 to -40.60
	Estimation Comments	Represents the least squares means difference from Placebo

Adverse Events

Time Frame	17 months
Adverse Event Reporting Description	The Efficacy population was comprised of 807 (Placebo) and 810 (Inclisiran) for a toal of 1617 subjects. The Safety population consisted of 804 (Placebo) and 811 (Inclisiran). The reason for this discrepancy is because two randomized subjects (Placebo) were not dosed, so were randomized in error. In addition, a placebo subject received inclisiran at Day 450 so was reallocated into the inclisiran group for safety as per the definition.

Arm/Group Title	Inclisiran	Placebo
Arm/Group Description	Inclisiran sodium 300 milligrams (m...	Placebo (1.5 mL) will be administer...
Arm/Group Description	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) in 1.5 milliliters (mL) will be administered as a SC injection on Day 1, Day 90, and then every 6 months Inclisiran Sodium: Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.	Placebo (1.5 mL) will be administered as a SC injection of saline solution on Day 1, Day 90, and then every 6 months Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).
All-Cause Mortality
	Inclisiran	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	14/811 (1.73%)	15/804 (1.87%)
Serious Adverse Events Serious Adverse Events
	Inclisiran	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	181/811 (22.32%)	181/804 (22.51%)
Blood and lymphatic system disorders
Anaemia ^† 1	1/811 (0.12%)	1/804 (0.12%)
Lymphadenopathy mediastinal ^† 1	0/811 (0.00%)	1/804 (0.12%)
Cardiac disorders
Acute coronary syndrome ^† 1	1/811 (0.12%)	2/804 (0.25%)
Acute myocardial infarction ^† 1	5/811 (0.62%)	18/804 (2.24%)
Angina pectoris ^† 1	14/811 (1.73%)	13/804 (1.62%)
Angina unstable ^† 1	11/811 (1.36%)	11/804 (1.37%)
Aortic valve stenosis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Arrhythmia ^† 1	0/811 (0.00%)	1/804 (0.12%)
Atrial fibrillation ^† 1	10/811 (1.23%)	6/804 (0.75%)
Atrial flutter ^† 1	1/811 (0.12%)	0/804 (0.00%)
Atrioventricular block complete ^† 1	1/811 (0.12%)	0/804 (0.00%)
Atrioventricular block second degree ^† 1	0/811 (0.00%)	2/804 (0.25%)
Bradycardia ^† 1	1/811 (0.12%)	0/804 (0.00%)
Cardiac arrest ^† 1	3/811 (0.37%)	0/804 (0.00%)
Cardiac failure ^† 1	3/811 (0.37%)	6/804 (0.75%)
Cardiac failure chronic ^† 1	1/811 (0.12%)	2/804 (0.25%)
Cardiac failure congestive ^† 1	5/811 (0.62%)	2/804 (0.25%)
Cardiomyopathy ^† 1	1/811 (0.12%)	0/804 (0.00%)
Coronary artery disease ^† 1	8/811 (0.99%)	11/804 (1.37%)
Coronary artery insufficiency ^† 1	1/811 (0.12%)	0/804 (0.00%)
Coronary artery occlusion ^† 1	1/811 (0.12%)	1/804 (0.12%)
Coronary artery stenosis ^† 1	1/811 (0.12%)	1/804 (0.12%)
Hypertensive heart disease ^† 1	0/811 (0.00%)	1/804 (0.12%)
Left ventricular dysfunction ^† 1	0/811 (0.00%)	1/804 (0.12%)
Left ventricular failure ^† 1	1/811 (0.12%)	0/804 (0.00%)
Mitral valve incompetence ^† 1	2/811 (0.25%)	0/804 (0.00%)
Myocardial infarction ^† 1	5/811 (0.62%)	4/804 (0.50%)
Myocardial ischaemia ^† 1	4/811 (0.49%)	5/804 (0.62%)
Palpitations ^† 1	1/811 (0.12%)	0/804 (0.00%)
Paroxysmal arrhythmia ^† 1	0/811 (0.00%)	1/804 (0.12%)
Pericardial effusion ^† 1	0/811 (0.00%)	1/804 (0.12%)
Silent myocardial infarction ^† 1	0/811 (0.00%)	1/804 (0.12%)
Supraventricular tachycardia ^† 1	1/811 (0.12%)	0/804 (0.00%)
Ventricular fibrillation ^† 1	1/811 (0.12%)	0/804 (0.00%)
Ventricular tachycardia ^† 1	1/811 (0.12%)	1/804 (0.12%)
Ear and labyrinth disorders
Vertigo ^† 1	0/811 (0.00%)	1/804 (0.12%)
Endocrine disorders
Hypopituitarism ^† 1	1/811 (0.12%)	0/804 (0.00%)
Eye disorders
Cataract ^† 1	1/811 (0.12%)	0/804 (0.00%)
Retinal detachment ^† 1	1/811 (0.12%)	0/804 (0.00%)
Gastrointestinal disorders
Abdominal pain ^† 1	1/811 (0.12%)	0/804 (0.00%)
Abdominal pain upper ^† 1	1/811 (0.12%)	0/804 (0.00%)
Ascites ^† 1	0/811 (0.00%)	1/804 (0.12%)
Chronic gastritis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Colitis ischaemic ^† 1	0/811 (0.00%)	1/804 (0.12%)
Constipation ^† 1	1/811 (0.12%)	0/804 (0.00%)
Diaphragmatic hernia ^† 1	1/811 (0.12%)	0/804 (0.00%)
Diarrhoea ^† 1	0/811 (0.00%)	1/804 (0.12%)
Diverticulum intestinal ^† 1	0/811 (0.00%)	1/804 (0.12%)
Diverticulum intestinal haemorrhagic ^† 1	0/811 (0.00%)	1/804 (0.12%)
Erosive oesophagitis ^† 1	0/811 (0.00%)	1/804 (0.12%)
Gastritis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Gastritis erosive ^† 1	0/811 (0.00%)	1/804 (0.12%)
Gastrointestinal haemorrhage ^† 1	1/811 (0.12%)	0/804 (0.00%)
Gastrooesophageal reflux disease ^† 1	1/811 (0.12%)	1/804 (0.12%)
Haemorrhoids ^† 1	1/811 (0.12%)	0/804 (0.00%)
Ileus paralytic ^† 1	1/811 (0.12%)	0/804 (0.00%)
Incarcerated umbilical hernia ^† 1	0/811 (0.00%)	1/804 (0.12%)
Inguinal hernia ^† 1	2/811 (0.25%)	2/804 (0.25%)
Large intestine polyp ^† 1	1/811 (0.12%)	2/804 (0.25%)
Oesophageal spasm ^† 1	1/811 (0.12%)	0/804 (0.00%)
Pancreatitis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Pancreatitis acute ^† 1	0/811 (0.00%)	1/804 (0.12%)
Pancreatitis chronic ^† 1	0/811 (0.00%)	1/804 (0.12%)
Pancreatitis necrotising ^† 1	1/811 (0.12%)	0/804 (0.00%)
Peptic ulcer ^† 1	0/811 (0.00%)	1/804 (0.12%)
Rectal haemorrhage ^† 1	1/811 (0.12%)	1/804 (0.12%)
Rectal prolapse ^† 1	1/811 (0.12%)	0/804 (0.00%)
Volvulus ^† 1	1/811 (0.12%)	0/804 (0.00%)
General disorders
Cardiac death ^† 1	0/811 (0.00%)	1/804 (0.12%)
Chest pain ^† 1	1/811 (0.12%)	0/804 (0.00%)
Death ^† 1	1/811 (0.12%)	2/804 (0.25%)
Exercise tolerance decreased ^† 1	0/811 (0.00%)	1/804 (0.12%)
Impaired healing ^† 1	0/811 (0.00%)	1/804 (0.12%)
Non-cardiac chest pain ^† 1	4/811 (0.49%)	8/804 (1.00%)
Sudden cardiac death ^† 1	1/811 (0.12%)	1/804 (0.12%)
Vascular stent occlusion ^† 1	1/811 (0.12%)	0/804 (0.00%)
Vascular stent restenosis ^† 1	0/811 (0.00%)	1/804 (0.12%)
Hepatobiliary disorders
Biliary dilatation ^† 1	1/811 (0.12%)	0/804 (0.00%)
Cholecystitis ^† 1	0/811 (0.00%)	2/804 (0.25%)
Cholecystitis acute ^† 1	3/811 (0.37%)	1/804 (0.12%)
Cholelithiasis ^† 1	3/811 (0.37%)	2/804 (0.25%)
Immune system disorders
Sarcoidosis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Infections and infestations
Abscess limb ^† 1	1/811 (0.12%)	0/804 (0.00%)
Appendicitis ^† 1	2/811 (0.25%)	2/804 (0.25%)
Biliary sepsis ^† 1	1/811 (0.12%)	1/804 (0.12%)
Bronchitis ^† 1	0/811 (0.00%)	2/804 (0.25%)
Cellulitis ^† 1	2/811 (0.25%)	1/804 (0.12%)
Chest wall abscess ^† 1	0/811 (0.00%)	1/804 (0.12%)
Device related sepsis ^† 1	0/811 (0.00%)	1/804 (0.12%)
Encephalitis ^† 1	0/811 (0.00%)	1/804 (0.12%)
Erysipelas ^† 1	1/811 (0.12%)	0/804 (0.00%)
Gallbladder abscess ^† 1	1/811 (0.12%)	0/804 (0.00%)
Gallbladder empyema ^† 1	0/811 (0.00%)	1/804 (0.12%)
Gangrene ^† 1	1/811 (0.12%)	0/804 (0.00%)
Infectious pleural effusion ^† 1	1/811 (0.12%)	1/804 (0.12%)
Infective exacerbation of chronic obstructive airways disease ^† 1	1/811 (0.12%)	2/804 (0.25%)
Influenza ^† 1	1/811 (0.12%)	0/804 (0.00%)
Intervertebral discitis ^† 1	0/811 (0.00%)	1/804 (0.12%)
Lower respiratory tract infection ^† 1	3/811 (0.37%)	3/804 (0.37%)
Neuroborreliosis ^† 1	0/811 (0.00%)	1/804 (0.12%)
Pathogen resistance ^† 1	0/811 (0.00%)	1/804 (0.12%)
Pneumonia ^† 1	9/811 (1.11%)	7/804 (0.87%)
Pneumonia pneumococcal ^† 1	1/811 (0.12%)	0/804 (0.00%)
Postoperative wound infection ^† 1	0/811 (0.00%)	2/804 (0.25%)
Sepsis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Septic shock ^† 1	0/811 (0.00%)	1/804 (0.12%)
Sialoadenitis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Staphylococcal sepsis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Urinary tract infection ^† 1	3/811 (0.37%)	1/804 (0.12%)
Wound infection ^† 1	1/811 (0.12%)	0/804 (0.00%)
Injury, poisoning and procedural complications
Acetabulum fracture ^† 1	1/811 (0.12%)	0/804 (0.00%)
Ankle fracture ^† 1	0/811 (0.00%)	1/804 (0.12%)
Arterial bypass occlusion ^† 1	0/811 (0.00%)	1/804 (0.12%)
Coronary vascular graft occlusion ^† 1	0/811 (0.00%)	1/804 (0.12%)
Craniocerebral injury ^† 1	0/811 (0.00%)	1/804 (0.12%)
Fall ^† 1	0/811 (0.00%)	1/804 (0.12%)
Femoral neck fracture ^† 1	2/811 (0.25%)	1/804 (0.12%)
Head injury ^† 1	0/811 (0.00%)	1/804 (0.12%)
Incision site pain ^† 1	1/811 (0.12%)	0/804 (0.00%)
Joint injury ^† 1	1/811 (0.12%)	0/804 (0.00%)
Limb injury ^† 1	0/811 (0.00%)	1/804 (0.12%)
Peripheral arterial reocclusion ^† 1	0/811 (0.00%)	1/804 (0.12%)
Periprocedural myocardial infarction ^† 1	0/811 (0.00%)	1/804 (0.12%)
Post procedural complication ^† 1	0/811 (0.00%)	1/804 (0.12%)
Procedural hypotension ^† 1	1/811 (0.12%)	0/804 (0.00%)
Procedural pain ^† 1	0/811 (0.00%)	1/804 (0.12%)
Radius fracture ^† 1	1/811 (0.12%)	0/804 (0.00%)
Rib fracture ^† 1	0/811 (0.00%)	1/804 (0.12%)
Soft tissue injury ^† 1	1/811 (0.12%)	0/804 (0.00%)
Spinal fracture ^† 1	1/811 (0.12%)	0/804 (0.00%)
Subdural haematoma ^† 1	0/811 (0.00%)	3/804 (0.37%)
Traumatic fracture ^† 1	1/811 (0.12%)	0/804 (0.00%)
Wound ^† 1	0/811 (0.00%)	1/804 (0.12%)
Investigations
Liver function test increased ^† 1	0/811 (0.00%)	1/804 (0.12%)
Metabolism and nutrition disorders
Dehydration ^† 1	1/811 (0.12%)	0/804 (0.00%)
Diabetes mellitus ^† 1	2/811 (0.25%)	1/804 (0.12%)
Diabetic ketoacidosis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Hyperglycaemia ^† 1	1/811 (0.12%)	1/804 (0.12%)
Hypoglycaemia ^† 1	2/811 (0.25%)	0/804 (0.00%)
Hypovolaemia ^† 1	1/811 (0.12%)	0/804 (0.00%)
Type 2 diabetes mellitus ^† 1	0/811 (0.00%)	1/804 (0.12%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	2/811 (0.25%)	1/804 (0.12%)
Arthritis ^† 1	0/811 (0.00%)	1/804 (0.12%)
Arthropathy ^† 1	0/811 (0.00%)	1/804 (0.12%)
Back pain ^† 1	1/811 (0.12%)	0/804 (0.00%)
Chondrocalcinosis pyrophosphate ^† 1	1/811 (0.12%)	0/804 (0.00%)
Costochondritis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Facet joint syndrome ^† 1	1/811 (0.12%)	0/804 (0.00%)
Inclusion body myositis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Intervertebral disc degeneration ^† 1	0/811 (0.00%)	1/804 (0.12%)
Intervertebral disc protrusion ^† 1	0/811 (0.00%)	2/804 (0.25%)
Intervertebral disc space narrowing ^† 1	1/811 (0.12%)	0/804 (0.00%)
Lumbar spinal stenosis ^† 1	0/811 (0.00%)	2/804 (0.25%)
Musculoskeletal pain ^† 1	1/811 (0.12%)	0/804 (0.00%)
Myalgia ^† 1	0/811 (0.00%)	1/804 (0.12%)
Osteoarthritis ^† 1	3/811 (0.37%)	3/804 (0.37%)
Pain in extremity ^† 1	1/811 (0.12%)	0/804 (0.00%)
Periarthritis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Psoriatic arthropathy ^† 1	1/811 (0.12%)	0/804 (0.00%)
Rotator cuff syndrome ^† 1	2/811 (0.25%)	0/804 (0.00%)
Soft tissue necrosis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Spinal osteoarthritis ^† 1	0/811 (0.00%)	1/804 (0.12%)
Spondylolisthesis ^† 1	0/811 (0.00%)	1/804 (0.12%)
Systemic lupus erythematosus ^† 1	0/811 (0.00%)	1/804 (0.12%)
Undifferentiated connective tissue disease ^† 1	1/811 (0.12%)	0/804 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia ^† 1	1/811 (0.12%)	0/804 (0.00%)
Adenocarcinoma gastric ^† 1	1/811 (0.12%)	1/804 (0.12%)
Bladder cancer ^† 1	1/811 (0.12%)	1/804 (0.12%)
Bladder neoplasm ^† 1	0/811 (0.00%)	1/804 (0.12%)
Bladder transitional cell carcinoma ^† 1	0/811 (0.00%)	2/804 (0.25%)
Bladder transitional cell carcinoma recurrent ^† 1	0/811 (0.00%)	1/804 (0.12%)
Carcinoid tumour of the stomach ^† 1	1/811 (0.12%)	0/804 (0.00%)
Clear cell renal cell carcinoma ^† 1	0/811 (0.00%)	1/804 (0.12%)
Colon cancer ^† 1	0/811 (0.00%)	1/804 (0.12%)
Endometrial adenocarcinoma ^† 1	1/811 (0.12%)	0/804 (0.00%)
Gastrointestinal carcinoma ^† 1	0/811 (0.00%)	1/804 (0.12%)
Hepatocellular carcinoma ^† 1	0/811 (0.00%)	1/804 (0.12%)
Intestinal adenocarcinoma ^† 1	1/811 (0.12%)	0/804 (0.00%)
Laryngeal cancer stage IV ^† 1	0/811 (0.00%)	1/804 (0.12%)
Lentigo maligna ^† 1	0/811 (0.00%)	1/804 (0.12%)
Linitis plastica ^† 1	0/811 (0.00%)	1/804 (0.12%)
Lung carcinoma cell type unspecified recurrent ^† 1	1/811 (0.12%)	0/804 (0.00%)
Lung neoplasm ^† 1	0/811 (0.00%)	1/804 (0.12%)
Lung neoplasm malignant ^† 1	2/811 (0.25%)	0/804 (0.00%)
Metastases to liver ^† 1	1/811 (0.12%)	0/804 (0.00%)
Metastatic carcinoma of the bladder ^† 1	0/811 (0.00%)	1/804 (0.12%)
Non-Hodgkin's lymphoma ^† 1	1/811 (0.12%)	0/804 (0.00%)
Oesophageal carcinoma ^† 1	1/811 (0.12%)	0/804 (0.00%)
Oral neoplasm ^† 1	1/811 (0.12%)	0/804 (0.00%)
Peripheral nerve sheath tumour malignant ^† 1	0/811 (0.00%)	1/804 (0.12%)
Prostate cancer ^† 1	1/811 (0.12%)	6/804 (0.75%)
Prostate cancer metastatic ^† 1	0/811 (0.00%)	1/804 (0.12%)
Rectal adenocarcinoma ^† 1	1/811 (0.12%)	0/804 (0.00%)
Renal cancer metastatic ^† 1	1/811 (0.12%)	0/804 (0.00%)
Renal cell carcinoma ^† 1	0/811 (0.00%)	1/804 (0.12%)
Salivary gland cancer ^† 1	1/811 (0.12%)	0/804 (0.00%)
Squamous cell carcinoma of the cervix ^† 1	1/811 (0.12%)	0/804 (0.00%)
Tracheal neoplasm ^† 1	0/811 (0.00%)	1/804 (0.12%)
Nervous system disorders
Brain injury ^† 1	1/811 (0.12%)	1/804 (0.12%)
Carotid artery stenosis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Cerebral infarction ^† 1	1/811 (0.12%)	2/804 (0.25%)
Dementia Alzheimer's type ^† 1	1/811 (0.12%)	0/804 (0.00%)
Facial paralysis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Generalised tonic-clonic seizure ^† 1	0/811 (0.00%)	1/804 (0.12%)
Haemorrhagic stroke ^† 1	0/811 (0.00%)	1/804 (0.12%)
Intracranial venous sinus thrombosis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Ischaemic stroke ^† 1	1/811 (0.12%)	3/804 (0.37%)
Lacunar stroke ^† 1	0/811 (0.00%)	2/804 (0.25%)
Loss of consciousness ^† 1	1/811 (0.12%)	0/804 (0.00%)
Neuropathy peripheral ^† 1	0/811 (0.00%)	1/804 (0.12%)
Peripheral sensorimotor neuropathy ^† 1	0/811 (0.00%)	1/804 (0.12%)
Presyncope ^† 1	0/811 (0.00%)	1/804 (0.12%)
Sciatica ^† 1	1/811 (0.12%)	1/804 (0.12%)
Seizure ^† 1	0/811 (0.00%)	2/804 (0.25%)
Syncope ^† 1	1/811 (0.12%)	2/804 (0.25%)
Transient ischaemic attack ^† 1	3/811 (0.37%)	1/804 (0.12%)
Product Issues
Device loosening ^† 1	1/811 (0.12%)	0/804 (0.00%)
Psychiatric disorders
Depression ^† 1	1/811 (0.12%)	0/804 (0.00%)
Suicide attempt ^† 1	0/811 (0.00%)	1/804 (0.12%)
Renal and urinary disorders
Acute kidney injury ^† 1	5/811 (0.62%)	1/804 (0.12%)
Calculus urinary ^† 1	0/811 (0.00%)	1/804 (0.12%)
Chronic kidney disease ^† 1	0/811 (0.00%)	1/804 (0.12%)
End stage renal disease ^† 1	1/811 (0.12%)	0/804 (0.00%)
Glomerulonephritis membranous ^† 1	1/811 (0.12%)	0/804 (0.00%)
Haematuria ^† 1	0/811 (0.00%)	1/804 (0.12%)
Nephrolithiasis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Nephrotic syndrome ^† 1	1/811 (0.12%)	0/804 (0.00%)
Renal colic ^† 1	1/811 (0.12%)	0/804 (0.00%)
Urethral stenosis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Reproductive system and breast disorders
Benign prostatic hyperplasia ^† 1	1/811 (0.12%)	2/804 (0.25%)
Pelvic prolapse ^† 1	0/811 (0.00%)	1/804 (0.12%)
Prostatomegaly ^† 1	0/811 (0.00%)	1/804 (0.12%)
Vaginal prolapse ^† 1	1/811 (0.12%)	0/804 (0.00%)
Respiratory, thoracic and mediastinal disorders
Asthma ^† 1	3/811 (0.37%)	1/804 (0.12%)
Choking ^† 1	0/811 (0.00%)	1/804 (0.12%)
Chronic obstructive pulmonary disease ^† 1	3/811 (0.37%)	3/804 (0.37%)
Dyspnoea ^† 1	1/811 (0.12%)	0/804 (0.00%)
Dyspnoea exertional ^† 1	1/811 (0.12%)	0/804 (0.00%)
Emphysema ^† 1	0/811 (0.00%)	1/804 (0.12%)
Nasal polyps ^† 1	1/811 (0.12%)	0/804 (0.00%)
Pleural effusion ^† 1	1/811 (0.12%)	0/804 (0.00%)
Pulmonary embolism ^† 1	2/811 (0.25%)	0/804 (0.00%)
Pulmonary fibrosis ^† 1	0/811 (0.00%)	1/804 (0.12%)
Pulmonary oedema ^† 1	0/811 (0.00%)	1/804 (0.12%)
Sleep apnoea syndrome ^† 1	1/811 (0.12%)	0/804 (0.00%)
Skin and subcutaneous tissue disorders
Pyoderma gangrenosum ^† 1	1/811 (0.12%)	0/804 (0.00%)
Surgical and medical procedures
Leg amputation ^† 1	1/811 (0.12%)	0/804 (0.00%)
Vascular disorders
Aortic aneurysm ^† 1	0/811 (0.00%)	2/804 (0.25%)
Aortic dissection ^† 1	1/811 (0.12%)	0/804 (0.00%)
Aortic stenosis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Blood pressure inadequately controlled ^† 1	1/811 (0.12%)	0/804 (0.00%)
Circulatory collapse ^† 1	0/811 (0.00%)	1/804 (0.12%)
Deep vein thrombosis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Extremity necrosis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Granulomatosis with polyangiitis ^† 1	1/811 (0.12%)	0/804 (0.00%)
Hypertension ^† 1	2/811 (0.25%)	2/804 (0.25%)
Hypotension ^† 1	0/811 (0.00%)	1/804 (0.12%)
Iliac artery embolism ^† 1	0/811 (0.00%)	1/804 (0.12%)
Orthostatic hypotension ^† 1	1/811 (0.12%)	1/804 (0.12%)
Peripheral arterial occlusive disease ^† 1	7/811 (0.86%)	8/804 (1.00%)
Peripheral artery occlusion ^† 1	0/811 (0.00%)	1/804 (0.12%)
Peripheral artery stenosis ^† 1	0/811 (0.00%)	1/804 (0.12%)
Peripheral ischaemia ^† 1	0/811 (0.00%)	2/804 (0.25%)
Peripheral vascular disorder ^† 1	1/811 (0.12%)	1/804 (0.12%)
Thromboangiitis obliterans ^† 1	1/811 (0.12%)	0/804 (0.00%)
Vasculitis ^† 1	1/811 (0.12%)	0/804 (0.00%)
1 Term from vocabulary, MedDRA 20.1 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Inclisiran	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	331/811 (40.81%)	319/804 (39.68%)
Infections and infestations
Nasopharyngitis ^† 1	91/811 (11.22%)	90/804 (11.19%)
Upper respiratory tract infection ^† 1	52/811 (6.41%)	49/804 (6.09%)
Metabolism and nutrition disorders
Diabetes mellitus ^† 1	88/811 (10.85%)	94/804 (11.69%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	47/811 (5.80%)	32/804 (3.98%)
Vascular disorders
Hypertension ^† 1	53/811 (6.54%)	54/804 (6.72%)
1 Term from vocabulary, MedDRA 20.1 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

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Name/Title:	Vice-President, Regulatory Operations
Organization:	Novartis
Phone:	973-985-0597
EMail:	frank.bosley@novartis.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ray KK, Wright RS, Kallend D, Koenig W, Leiter LA, Raal FJ, Bisch JA, Richardson T, Jaros M, Wijngaard PLJ, Kastelein JJP; ORION-10 and ORION-11 Investigators. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020 Apr 16;382(16):1507-1519. doi: 10.1056/NEJMoa1912387. Epub 2020 Mar 18.

Layout table for additonal information

Responsible Party:	The Medicines Company
ClinicalTrials.gov Identifier:	NCT03400800
Other Study ID Numbers:	MDCO-PCS-17-08
First Submitted:	January 9, 2018
First Posted:	January 17, 2018
Results First Submitted:	June 30, 2020
Results First Posted:	August 21, 2020
Last Update Posted:	August 21, 2020

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