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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
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
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Inclisiran Placebo
Hide 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
Arm/Group Title Inclisiran Placebo Total
Hide 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
Hide 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
1.Primary Outcome
Title Percentage Change in LDL-C From Baseline to Day 510
Hide Description [Not Specified]
Time Frame Baseline, Day 510
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Inclisiran Placebo
Hide 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)
Hide 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
Hide Description [Not Specified]
Time Frame Baseline, Day 90 to Day 540
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Inclisiran Placebo
Hide 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)
Hide 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
Hide Description [Not Specified]
Time Frame Baseline, Day 510
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Inclisiran Placebo
Hide 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)
Hide 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
Hide Description [Not Specified]
Time Frame Baseline, Day 90 to Day 540
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Inclisiran Placebo
Hide 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)
Hide 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
Hide Description [Not Specified]
Time Frame Baseline, Day 510
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Inclisiran Placebo
Hide 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)
Hide 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
Hide Description [Not Specified]
Time Frame Baseline, Day 510
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Inclisiran Placebo
Hide 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)
Hide 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
Hide Description [Not Specified]
Time Frame Baseline, Day 510
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Inclisiran Placebo
Hide 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)
Hide 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
Hide Description [Not Specified]
Time Frame Baseline, Day 510
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Inclisiran Placebo
Hide 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)
Hide 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
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
Hide 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%) 
Hide 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
Hide 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
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
Layout table for Results Point of Contact information
Name/Title: Vice-President, Regulatory Operations
Organization: Novartis
Phone: 973-985-0597
EMail: frank.bosley@novartis.com
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