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Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol (ORION-10)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT03399370

Recruitment Status : Completed

First Posted : January 16, 2018

Results First Posted : October 5, 2020

Last Update Posted : October 5, 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 Elevated Cholesterol
Interventions	Drug: Inclisiran Sodium Drug: Placebo
Enrollment	1561

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Inclisiran	Saline Solution
Arm/Group Description	Inclisiran sodium 300 milligrams (m...	Placebo will be administered as a S...
Arm/Group Description	Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90, then every 6 months. Inclisiran Sodium: Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.	Placebo will be administered as a SC injection of saline solution on Day 1, Day 90, then every 6 months. Placebo: Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).
Period Title: Overall Study
Started	781	780
Completed	721	694
Not Completed	60	86

Baseline Characteristics

Arm/Group Title		Inclisiran	Placebo	Total
Arm/Group Description		Inclisiran sodium 300 milligrams (m...	Placebo will be administered as a S...	Total of all reporting groups
Arm/Group Description		Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90, then every 6 months. Inclisiran Sodium: Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.	Placebo will be administered as a SC injection of saline solution on Day 1, Day 90, 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		781	780	1561
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	781 participants	780 participants	1561 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	297 38.0%	333 42.7%	630 40.4%
	>=65 years	484 62.0%	447 57.3%	931 59.6%
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	781 participants	780 participants	1561 participants
		66.4 (8.90)	65.7 (8.89)	66.0 (8.90)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	781 participants	780 participants	1561 participants
	Female	246 31.5%	232 29.7%	478 30.6%
	Male	535 68.5%	548 70.3%	1083 69.4%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	781 participants	780 participants	1561 participants
	American Indian or Alaska Native	2 0.3%	4 0.5%	6 0.4%
	Asian	9 1.2%	1 0.1%	10 0.6%
	Native Hawaiian or Other Pacific Islander	7 0.9%	3 0.4%	10 0.6%
	Black or African American	110 14.1%	87 11.2%	197 12.6%
	White	653 83.6%	685 87.8%	1338 85.7%
	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
United States	Number Analyzed	781 participants	780 participants	1561 participants
United States		781	780	1561

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

Intent-to-treat (ITT) population


Arm/Group Title	Inclisiran	Placebo
Arm/Group Description:	Inclisiran sodium 300 milligrams (m...	Placebo administered as a subcutane...
Arm/Group Description:	Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90, then every 6 months. Inclisiran Sodium: Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.	Placebo 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	781	780
Least Squares Mean (95% Confidence Interval) Unit of Measure: percent change
	-56.34 (-58.35 to -54.34)	1.30 (-1.24 to 3.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	LS Mean Difference (95% CI) from Placebo

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	Mean Difference (Final Values)
	Estimated Value	-57.64
	Confidence Interval	(2-Sided) 95% -60.86 to -54.43
	Estimation Comments	Represents the least squares mean difference from Placebo

2.Primary Outcome


Title	Time-adjusted Percentage Change in LDL-C Levels From Baseline After Day 90 and up to Day 540
Description	Assessments performed at Baseline, Day 90, Day 540, time-adjusted perc...
Description	Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 540 reported
Time Frame	Baseline, Day 90 to Day 540

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population


Arm/Group Title	Inclisiran	Placebo
Arm/Group Description:	Inclisiran sodium 300 milligrams (m...	Placebo administered as a subcutane...
Arm/Group Description:	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo 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	781	790
Least Squares Mean (95% Confidence Interval) Unit of Measure: percent change
	-51.27 (-53.00 to -49.54)	2.51 (0.77 to 4.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	LS Mean Difference (95% CI) from Placebo

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	-53.78
	Confidence Interval	(2-Sided) 95% -56.23 to -51.33
	Estimation Comments	Represents the least squares mean 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

Intent-to-treat (ITT) population


Arm/Group Title	Inclisiran	Placebo
Arm/Group Description:	Inclisiran sodium 300 milligrams (m...	Placebo administered as a subcutane...
Arm/Group Description:	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo 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	781	780
Least Squares Mean (95% Confidence Interval) Unit of Measure: mg/dL
	-56.18 (-58.47 to -53.90)	-2.06 (-4.36 to 0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inclisiran, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	LS Mean Difference (95% CI) from Placebo

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	-54.12
	Confidence Interval	(2-Sided) 95% -57.37 to -50.88
	Estimation Comments	Represents the least squares mean 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	Assessments performed at Baseline, Day 90, Day 540, time-adjusted perc...
Description	Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 540 reported
Time Frame	Baseline, Day 90 to Day 540

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population


Arm/Group Title	Inclisiran	Placebo
Arm/Group Description:	Inclisiran sodium 300 milligrams (m...	Placebo administered as a subcutane...
Arm/Group Description:	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo 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	781	780
Least Squares Mean (95% Confidence Interval) Unit of Measure: mg/dL
	-53.66 (-55.41 to -51.92)	-0.39 (-2.14 to 1.37)

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	-53.28
	Confidence Interval	(2-Sided) 95% -55.75 to -50.80
	Estimation Comments	Represents the least squares mean 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

Intent-to-treat (ITT) population


Arm/Group Title	Inclisiran	Placebo
Arm/Group Description:	Inclisiran sodium 300 milligrams (m...	Placebo administered as a subcutane...
Arm/Group Description:	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo 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	781	780
Least Squares Mean (95% Confidence Interval) Unit of Measure: percent change
	-69.78 (-73.88 to -65.67)	13.52 (9.28 to 17.77)

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	-83.80
	Confidence Interval	(2-Sided) 95% -89.25 to -77.34
	Estimation Comments	Represents the least squares mean 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

Intent-to-treat (ITT) population


Arm/Group Title	Inclisiran	Placebo
Arm/Group Description:	Inclisiran sodium 300 milligrams (m...	Placebo administered as a subcutane...
Arm/Group Description:	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo 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	781	781
Least Squares Mean (95% Confidence Interval) Unit of Measure: percent change
	-33.56 (-35.09 to -32.03)	-0.42 (-1.95 to 1.11)

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	-33.13
	Confidence Interval	(2-Sided) 95% -35.30 to -30.97
	Estimation Comments	Represents the least squares mean 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

Intent-to-treat (ITT) population


Arm/Group Title	Inclisiran	Placebo
Arm/Group Description:	Inclisiran sodium 300 milligrams (m...	Placebo administered as a subcutane...
Arm/Group Description:	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo 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	781	780
Least Squares Mean (95% Confidence Interval) Unit of Measure: percent change
	-44.81 (-46.52 to -43.10)	-1.72 (-3.46 to 0.02)

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	Mean Difference (Final Values)
	Estimated Value	-43.09
	Confidence Interval	(2-Sided) 95% -45.50 to -40.67
	Estimation Comments	Represents the least squares mean 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

Intent-to-treat (ITT) population


Arm/Group Title	Inclisiran	Placebo
Arm/Group Description:	Inclisiran sodium 300 milligrams (m...	Placebo administered as a subcutane...
Arm/Group Description:	Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) administered as a subcutaneous injection on Day 1, Day 90, and then every 6 months.	Placebo 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	781	780
Least Squares Mean (95% Confidence Interval) Unit of Measure: percent change
	-47.41 (-49.44 to -45.38)	-0.05 (-2.08 to 1.99)

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	-47.36
	Confidence Interval	(2-Sided) 95% -50.25 to -44.47
	Estimation Comments	Represents the least squares mean difference from Placebo

Adverse Events

Time Frame	18 months
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Inclisiran	Saline Solution
Arm/Group Description	Inclisiran sodium 300 milligrams (m...	Placebo will be administered as a S...
Arm/Group Description	Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90, then every 6 months. Inclisiran Sodium: Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.	Placebo will be administered as a SC injection of saline solution on Day 1, Day 90, then every 6 months. Placebo: Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).
All-Cause Mortality
	Inclisiran	Saline Solution
	Affected / at Risk (%)	Affected / at Risk (%)
Total	12/781 (1.54%)	11/778 (1.41%)
Serious Adverse Events Serious Adverse Events
	Inclisiran	Saline Solution
	Affected / at Risk (%)	Affected / at Risk (%)
Total	175/781 (22.41%)	205/778 (26.35%)
Blood and lymphatic system disorders
Anaemia ^† 1	3/781 (0.38%)	1/778 (0.13%)
Haemorrhagic anaemia ^† 1	2/781 (0.26%)	0/778 (0.00%)
Iron deficiency anaemia ^† 1	0/781 (0.00%)	1/778 (0.13%)
Leukocytosis ^† 1	0/781 (0.00%)	1/778 (0.13%)
Leukopenia ^† 1	1/781 (0.13%)	0/778 (0.00%)
Thrombocytopenia ^† 1	1/781 (0.13%)	0/778 (0.00%)
Cardiac disorders
Acute coronary syndrome ^† 1	0/781 (0.00%)	2/778 (0.26%)
Acute myocardial infarction ^† 1	14/781 (1.79%)	12/778 (1.54%)
Angina pectoris ^† 1	6/781 (0.77%)	7/778 (0.90%)
Angina unstable ^† 1	4/781 (0.51%)	10/778 (1.29%)
Arteriosclerosis coronary artery ^† 1	0/781 (0.00%)	1/778 (0.13%)
Atrial fibrillation ^† 1	10/781 (1.28%)	8/778 (1.03%)
Atrial flutter ^† 1	0/781 (0.00%)	1/778 (0.13%)
Atrioventricular block ^† 1	2/781 (0.26%)	0/778 (0.00%)
Atrioventricular block complete ^† 1	1/781 (0.13%)	0/778 (0.00%)
Atrioventricular block second degree ^† 1	0/781 (0.00%)	1/778 (0.13%)
Bradycardia ^† 1	1/781 (0.13%)	2/778 (0.26%)
Cardiac arrest ^† 1	1/781 (0.13%)	1/778 (0.13%)
Cardiac failure ^† 1	0/781 (0.00%)	1/778 (0.13%)
Cardiac failure acute ^† 1	1/781 (0.13%)	1/778 (0.13%)
Cardiac failure congestive ^† 1	7/781 (0.90%)	20/778 (2.57%)
Cardio-respiratory arrest ^† 1	1/781 (0.13%)	0/778 (0.00%)
Cardiomyopathy ^† 1	2/781 (0.26%)	0/778 (0.00%)
Coronary artery disease ^† 1	15/781 (1.92%)	22/778 (2.83%)
Coronary artery occlusion ^† 1	1/781 (0.13%)	2/778 (0.26%)
Ischaemic cardiomyopathy ^† 1	1/781 (0.13%)	0/778 (0.00%)
Left ventricular failure ^† 1	3/781 (0.38%)	1/778 (0.13%)
Mitral valve incompetence ^† 1	0/781 (0.00%)	3/778 (0.39%)
Myocardial infarction ^† 1	6/781 (0.77%)	6/778 (0.77%)
Nodal arrythmia ^† 1	0/781 (0.00%)	1/778 (0.13%)
Palpitations ^† 1	0/781 (0.00%)	1/778 (0.13%)
Pericardial effusion ^† 1	0/781 (0.00%)	1/778 (0.13%)
Pericarditis ^† 1	0/781 (0.00%)	2/778 (0.26%)
Sinus node dysfunction ^† 1	0/781 (0.00%)	2/778 (0.26%)
Supraventricular tachycardia ^† 1	0/781 (0.00%)	2/778 (0.26%)
Tachycardia ^† 1	0/781 (0.00%)	1/778 (0.13%)
Ventricular extrasystoles ^† 1	1/781 (0.13%)	0/778 (0.00%)
Ventricular fibrillation ^† 1	0/781 (0.00%)	2/778 (0.26%)
Ventricular tachyarrhythmia ^† 1	1/781 (0.13%)	0/778 (0.00%)
Ventricular tachycardia ^† 1	2/781 (0.26%)	4/778 (0.51%)
Congenital, familial and genetic disorders
Atrial septal defect ^† 1	0/781 (0.00%)	1/778 (0.13%)
Endocrine disorders
Ectopic hyperthyroidism ^† 1	1/781 (0.13%)	0/778 (0.00%)
Eye disorders
Ophthalmic vein thrombosis ^† 1	0/781 (0.00%)	1/778 (0.13%)
Retinal artery occlusion ^† 1	1/781 (0.13%)	0/778 (0.00%)
Visual impairment ^† 1	0/781 (0.00%)	1/778 (0.13%)
Gastrointestinal disorders
Abdominal pain ^† 1	0/781 (0.00%)	1/778 (0.13%)
Abdominal pain upper ^† 1	1/781 (0.13%)	0/778 (0.00%)
Anal fistula ^† 1	0/781 (0.00%)	1/778 (0.13%)
Colitis ischaemic ^† 1	1/781 (0.13%)	2/778 (0.26%)
Constipation ^† 1	1/781 (0.13%)	0/778 (0.00%)
Diarrhoea ^† 1	0/781 (0.00%)	2/778 (0.26%)
Diverticulum ^† 1	0/781 (0.00%)	1/778 (0.13%)
Diverticulum intestinal haemorrhagic ^† 1	0/781 (0.00%)	1/778 (0.13%)
Duodenal polyp ^† 1	1/781 (0.13%)	0/778 (0.00%)
Enteritis ^† 1	0/781 (0.00%)	1/778 (0.13%)
Gastritis erosive ^† 1	1/781 (0.13%)	0/778 (0.00%)
Gastrointestinal haemorrhage ^† 1	0/781 (0.00%)	2/778 (0.26%)
Intestinal infarction ^† 1	0/781 (0.00%)	1/778 (0.13%)
Intestinal ischaemia ^† 1	0/781 (0.00%)	1/778 (0.13%)
Intestinal obstruction ^† 1	0/781 (0.00%)	1/778 (0.13%)
Larger intestine perforation ^† 1	0/781 (0.00%)	1/778 (0.13%)
Oesophageal varices haemorrhage ^† 1	1/781 (0.13%)	0/778 (0.00%)
Pancreatic mass ^† 1	0/781 (0.00%)	1/778 (0.13%)
Pancreatitis ^† 1	1/781 (0.13%)	0/778 (0.00%)
Rectal haemorrhage ^† 1	0/781 (0.00%)	1/778 (0.13%)
Retroperitoneal haemorrhage ^† 1	0/781 (0.00%)	1/778 (0.13%)
Small intestinal obstruction ^† 1	4/781 (0.51%)	0/778 (0.00%)
Upper gastrointestinal haemorrhage ^† 1	1/781 (0.13%)	1/778 (0.13%)
Vomiting ^† 1	0/781 (0.00%)	1/778 (0.13%)
General disorders
Asthenia ^† 1	0/781 (0.00%)	3/778 (0.39%)
Chest pain ^† 1	2/781 (0.26%)	3/778 (0.39%)
Death ^† 1	2/781 (0.26%)	1/778 (0.13%)
Gait disturbance ^† 1	0/781 (0.00%)	1/778 (0.13%)
Hypothermia ^† 1	0/781 (0.00%)	1/778 (0.13%)
Multiple organ dysfunction syndrome ^† 1	0/781 (0.00%)	1/778 (0.13%)
Non-cardiac chest pain ^† 1	10/781 (1.28%)	9/778 (1.16%)
Pyrexia ^† 1	1/781 (0.13%)	0/778 (0.00%)
Sensation of foreign body ^† 1	1/781 (0.13%)	0/778 (0.00%)
Ulcer haemorrhage ^† 1	0/781 (0.00%)	1/778 (0.13%)
Vascular stent restenosis ^† 1	0/781 (0.00%)	1/778 (0.13%)
Hepatobiliary disorders
Bile duct stone ^† 1	1/781 (0.13%)	1/778 (0.13%)
Cholecystitis ^† 1	0/781 (0.00%)	1/778 (0.13%)
Cholecystitis acute ^† 1	1/781 (0.13%)	2/778 (0.26%)
Cholelithiasis ^† 1	0/781 (0.00%)	2/778 (0.26%)
Hepatic cirrhosis ^† 1	1/781 (0.13%)	0/778 (0.00%)
Immune system disorders
Anaphylactic reaction ^† 1	0/781 (0.00%)	1/778 (0.13%)
Infections and infestations
Anal abscess ^† 1	1/781 (0.13%)	0/778 (0.00%)
Appendicitis ^† 1	2/781 (0.26%)	1/778 (0.13%)
Appendicitis perforated ^† 1	1/781 (0.13%)	0/778 (0.00%)
Arthritis infective ^† 1	1/781 (0.13%)	0/778 (0.00%)
Bacterial pyelonephritis ^† 1	0/781 (0.00%)	1/778 (0.13%)
Bronchitis ^† 1	2/781 (0.26%)	2/778 (0.26%)
Cavernous sinus thrombosis ^† 1	0/781 (0.00%)	1/778 (0.13%)
Cellulitis ^† 1	4/781 (0.51%)	2/778 (0.26%)
Clostridium difficile colitis ^† 1	1/781 (0.13%)	1/778 (0.13%)
Cystitis ^† 1	1/781 (0.13%)	0/778 (0.00%)
Device related infection ^† 1	1/781 (0.13%)	0/778 (0.00%)
Diabetic foot infection ^† 1	1/781 (0.13%)	0/778 (0.00%)
Diverticultis ^† 1	2/781 (0.26%)	2/778 (0.26%)
Escherichia bacteraemia ^† 1	1/781 (0.13%)	1/778 (0.13%)
Gangrene ^† 1	0/781 (0.00%)	1/778 (0.13%)
Gastroenteritis ^† 1	2/781 (0.26%)	0/778 (0.00%)
Gastroenteritis norovirus ^† 1	0/781 (0.00%)	1/778 (0.13%)
Infectious colitis ^† 1	0/781 (0.00%)	1/778 (0.13%)
Influenza ^† 1	2/781 (0.26%)	1/778 (0.13%)
Localised infection ^† 1	2/781 (0.26%)	0/778 (0.00%)
Osteomyelitis ^† 1	1/781 (0.13%)	2/778 (0.26%)
Osteomyelitis acute ^† 1	1/781 (0.13%)	0/778 (0.00%)
Periorbital cellulitis ^† 1	1/781 (0.13%)	0/778 (0.00%)
Periotinitis ^† 1	1/781 (0.13%)	0/778 (0.00%)
Pneumonia ^† 1	11/781 (1.41%)	9/778 (1.16%)
Pneumonia bacterial ^† 1	1/781 (0.13%)	0/778 (0.00%)
Pneumonia viral ^† 1	1/781 (0.13%)	0/778 (0.00%)
Post procedural infection ^† 1	1/781 (0.13%)	0/778 (0.00%)
Postoperative wound infection ^† 1	0/781 (0.00%)	1/778 (0.13%)
Pyelonephritis ^† 1	0/781 (0.00%)	1/778 (0.13%)
Sepsis ^† 1	6/781 (0.77%)	4/778 (0.51%)
Sepsis syndrome ^† 1	0/781 (0.00%)	1/778 (0.13%)
Septic shock ^† 1	1/781 (0.13%)	1/778 (0.13%)
Staphylococcal abscess ^† 1	1/781 (0.13%)	0/778 (0.00%)
Urinary tract infection ^† 1	0/781 (0.00%)	3/778 (0.39%)
Injury, poisoning and procedural complications
Accidental overdose ^† 1	0/781 (0.00%)	1/778 (0.13%)
Cardiac contusion ^† 1	0/781 (0.00%)	1/778 (0.13%)
Cardiac valve replacement complication ^† 1	0/781 (0.00%)	1/778 (0.13%)
Chemical burn ^† 1	1/781 (0.13%)	0/778 (0.00%)
Contusion ^† 1	1/781 (0.13%)	0/778 (0.00%)
Craniocerebral injury ^† 1	0/781 (0.00%)	1/778 (0.13%)
Facial bones fracture ^† 1	0/781 (0.00%)	1/778 (0.13%)
Fall ^† 1	2/781 (0.26%)	0/778 (0.00%)
Femoral neck fracture ^† 1	0/781 (0.00%)	2/778 (0.26%)
Foot fracture ^† 1	1/781 (0.13%)	0/778 (0.00%)
Gun shot wound ^† 1	0/781 (0.00%)	1/778 (0.13%)
Head injury ^† 1	1/781 (0.13%)	0/778 (0.00%)
Hip fracture ^† 1	0/781 (0.00%)	1/778 (0.13%)
Humerus fracture ^† 1	0/781 (0.00%)	1/778 (0.13%)
Incisional hernia, obstructive ^† 1	1/781 (0.13%)	0/778 (0.00%)
Joint dislocation ^† 1	1/781 (0.13%)	0/778 (0.00%)
Lumbar vertebral fracture ^† 1	1/781 (0.13%)	0/778 (0.00%)
Multiple injuries ^† 1	1/781 (0.13%)	0/778 (0.00%)
Occupational exposure to product ^† 1	1/781 (0.13%)	0/778 (0.00%)
Post procedural haematuria ^† 1	0/781 (0.00%)	1/778 (0.13%)
Post procedural hawmorrhage ^† 1	1/781 (0.13%)	0/778 (0.00%)
Procedural pain ^† 1	0/781 (0.00%)	1/778 (0.13%)
Rib fracture ^† 1	1/781 (0.13%)	1/778 (0.13%)
Road traffic accident ^† 1	1/781 (0.13%)	1/778 (0.13%)
Spinal compression fracture ^† 1	0/781 (0.00%)	1/778 (0.13%)
Subarachnoid haemorrhage ^† 1	0/781 (0.00%)	1/778 (0.13%)
Subdural haemorrhage ^† 1	0/781 (0.00%)	1/778 (0.13%)
Thoracic vertebral fracture ^† 1	0/781 (0.00%)	1/778 (0.13%)
Tibia fracture ^† 1	0/781 (0.00%)	1/778 (0.13%)
Vascular pseudoaneurysm ^† 1	1/781 (0.13%)	0/778 (0.00%)
Wrist fracture ^† 1	0/781 (0.00%)	1/778 (0.13%)
Investigations
Blood pressure increased ^† 1	0/781 (0.00%)	1/778 (0.13%)
Metabolism and nutrition disorders
Dehydration ^† 1	0/781 (0.00%)	2/778 (0.26%)
Diabetes Mellitus ^† 1	0/781 (0.00%)	2/778 (0.26%)
Diabetes mellitus inadequate control ^† 1	0/781 (0.00%)	2/778 (0.26%)
Diabetic ketoacidosis ^† 1	1/781 (0.13%)	1/778 (0.13%)
Fluid overload ^† 1	1/781 (0.13%)	0/778 (0.00%)
Gout ^† 1	0/781 (0.00%)	2/778 (0.26%)
Hypercalcaemia ^† 1	1/781 (0.13%)	0/778 (0.00%)
Hyperglycaemia ^† 1	3/781 (0.38%)	0/778 (0.00%)
Hyperkalaemia ^† 1	0/781 (0.00%)	1/778 (0.13%)
Hypoglycaemia ^† 1	1/781 (0.13%)	0/778 (0.00%)
Hypokalaemia ^† 1	1/781 (0.13%)	1/778 (0.13%)
Hyponatraemia ^† 1	0/781 (0.00%)	1/778 (0.13%)
Hypovolaemia ^† 1	1/781 (0.13%)	1/778 (0.13%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	2/781 (0.26%)	0/778 (0.00%)
Arthritis ^† 1	0/781 (0.00%)	1/778 (0.13%)
Back pain ^† 1	1/781 (0.13%)	2/778 (0.26%)
Cervical spinal stenosis ^† 1	0/781 (0.00%)	3/778 (0.39%)
Fracture malunion ^† 1	0/781 (0.00%)	1/778 (0.13%)
Intervertebral disc degeneration ^† 1	0/781 (0.00%)	1/778 (0.13%)
Lumbar spinal stenosis ^† 1	1/781 (0.13%)	4/778 (0.51%)
Muscular weakness ^† 1	0/781 (0.00%)	1/778 (0.13%)
Musculoskeletal pain ^† 1	0/781 (0.00%)	1/778 (0.13%)
Osteoarthritis ^† 1	2/781 (0.26%)	2/778 (0.26%)
Rhabdomyolysis ^† 1	0/781 (0.00%)	1/778 (0.13%)
Spinal column stenosis ^† 1	1/781 (0.13%)	1/778 (0.13%)
Spinal osteoarthritis ^† 1	0/781 (0.00%)	2/778 (0.26%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia ^† 1	1/781 (0.13%)	0/778 (0.00%)
Adenocarcinoma ^† 1	0/781 (0.00%)	1/778 (0.13%)
Adenocarcinoma of colon ^† 1	0/781 (0.00%)	1/778 (0.13%)
Bladder cancer ^† 1	1/781 (0.13%)	0/778 (0.00%)
Bladder transitional cell carcinoma ^† 1	0/781 (0.00%)	1/778 (0.13%)
Bowen's disease ^† 1	3/781 (0.38%)	0/778 (0.00%)
Breast cancer ^† 1	1/781 (0.13%)	0/778 (0.00%)
Breast cancer stage 1 ^† 1	0/781 (0.00%)	1/778 (0.13%)
Carcinoid tumour of the stomach ^† 1	0/781 (0.00%)	2/778 (0.26%)
Clear cell renal cell carcinoma ^† 1	0/781 (0.00%)	1/778 (0.13%)
Colon cancer metastatic ^† 1	0/781 (0.00%)	1/778 (0.13%)
Endometrial cancer ^† 1	0/781 (0.00%)	2/778 (0.26%)
Gastrointestinal lymphoma ^† 1	1/781 (0.13%)	0/778 (0.00%)
Gastrooesophageal cancer ^† 1	0/781 (0.00%)	1/778 (0.13%)
Hepatic cancer ^† 1	1/781 (0.13%)	0/778 (0.00%)
Invasive ductal breast carcinoma ^† 1	0/781 (0.00%)	1/778 (0.13%)
Liposarcoma recurrent ^† 1	0/781 (0.00%)	1/778 (0.13%)
Lung adenocarcinoma ^† 1	0/781 (0.00%)	3/778 (0.39%)
Malignant melanoma ^† 1	0/781 (0.00%)	1/778 (0.13%)
Meningioma ^† 1	0/781 (0.00%)	1/778 (0.13%)
Metastases to central nervous system ^† 1	1/781 (0.13%)	0/778 (0.00%)
Metastases to liver ^† 1	0/781 (0.00%)	2/778 (0.26%)
Myelodyplastic syndrome ^† 1	0/781 (0.00%)	1/778 (0.13%)
Non-small cell lung cancer ^† 1	1/781 (0.13%)	1/778 (0.13%)
Pancreatic carcinoma metastatic ^† 1	0/781 (0.00%)	1/778 (0.13%)
Prostate cancer ^† 1	4/781 (0.51%)	2/778 (0.26%)
Prostate cancer recurrent ^† 1	1/781 (0.13%)	1/778 (0.13%)
Renal cancer ^† 1	1/781 (0.13%)	0/778 (0.00%)
Renal cell carcinoma ^† 1	1/781 (0.13%)	0/778 (0.00%)
Squamous cell carcinoma ^† 1	3/781 (0.38%)	2/778 (0.26%)
Squamous cell carcinoma of lung ^† 1	2/781 (0.26%)	1/778 (0.13%)
Squamous cell carcinoma of skin ^† 1	5/781 (0.64%)	1/778 (0.13%)
Nervous system disorders
Carotid artery disease ^† 1	1/781 (0.13%)	1/778 (0.13%)
Carotid artery stenosis ^† 1	3/781 (0.38%)	2/778 (0.26%)
Cerebral haemorrhage ^† 1	1/781 (0.13%)	0/778 (0.00%)
Cerebral infarction ^† 1	1/781 (0.13%)	1/778 (0.13%)
Cerebrovascular accident ^† 1	4/781 (0.51%)	3/778 (0.39%)
Cerebrovascular disorder ^† 1	1/781 (0.13%)	0/778 (0.00%)
Cervical radiculopathy ^† 1	0/781 (0.00%)	2/778 (0.26%)
Demetia ^† 1	0/781 (0.00%)	1/778 (0.13%)
Dizziness ^† 1	3/781 (0.38%)	0/778 (0.00%)
Headache ^† 1	1/781 (0.13%)	1/778 (0.13%)
Hemiparesis ^† 1	0/781 (0.00%)	1/778 (0.13%)
Ischaemic stroke ^† 1	7/781 (0.90%)	4/778 (0.51%)
Metabolic encephalopathy ^† 1	0/781 (0.00%)	1/778 (0.13%)
Migraine ^† 1	1/781 (0.13%)	0/778 (0.00%)
Myelopathy ^† 1	0/781 (0.00%)	1/778 (0.13%)
Nerve compression ^† 1	0/781 (0.00%)	1/778 (0.13%)
Normal pressure hydrocephalus ^† 1	0/781 (0.00%)	2/778 (0.26%)
Presyncope ^† 1	2/781 (0.26%)	0/778 (0.00%)
Radiculopathy ^† 1	0/781 (0.00%)	1/778 (0.13%)
Seizure ^† 1	0/781 (0.00%)	1/778 (0.13%)
Spinal subdural haematoma ^† 1	0/781 (0.00%)	1/778 (0.13%)
Status migrainosus ^† 1	1/781 (0.13%)	0/778 (0.00%)
Syncope ^† 1	4/781 (0.51%)	7/778 (0.90%)
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	Saline Solution
	Affected / at Risk (%)	Affected / at Risk (%)
Total	247/781 (31.63%)	219/778 (28.15%)
Infections and infestations
Bronchitis ^† 1	46/781 (5.89%)	30/778 (3.86%)
Metabolism and nutrition disorders
Diabetes mellitus ^† 1	120/781 (15.36%)	108/778 (13.88%)
Musculoskeletal and connective tissue disorders
Back pain ^† 1	39/781 (4.99%)	39/778 (5.01%)
Vascular disorders
Hypertension ^† 1	42/781 (5.38%)	42/778 (5.40%)
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:	The Medicines Company
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.

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Responsible Party:	The Medicines Company
ClinicalTrials.gov Identifier:	NCT03399370
Other Study ID Numbers:	MDCO-PCS-17-04
First Submitted:	January 3, 2018
First Posted:	January 16, 2018
Results First Submitted:	July 1, 2020
Results First Posted:	October 5, 2020
Last Update Posted:	October 5, 2020