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Trial to Evaluate the Effect of ALN-PCSSC Treatment on Low Density Lipoprotein Cholesterol (LDL-C) (ORION-1)

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: NCT02597127
Recruitment Status : Completed
First Posted : November 5, 2015
Results First Posted : May 17, 2019
Last Update Posted : May 17, 2019
Sponsor:
Information provided by (Responsible Party):
The Medicines Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Atherosclerotic Cardiovascular Disease
Familial Hypercholesterolemia
Diabetes
Interventions Drug: ALN-PCSSC
Drug: Normal Saline
Enrollment 501
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Inclisiran 200 mg (Single-dose) Inclisiran 300 mg (Single-dose) Inclisiran 500 mg (Single-dose) Placebo (Single-dose) Inclisiran 100 mg (Double-dose) Inclisiran 200 mg (Double-dose) Inclisiran 300 mg (Double-dose) Placebo (Double-dose)
Hide Arm/Group Description 200 mg subcutaneous administration once at Day 1 300 mg subcutaneous administration once at Day 1 500 mg subcutaneous administration once at Day 1 Saline subcutaneous administration once at Day 1 100 mg subcutaneous administration at Day 1 and Day 90 200 mg subcutaneous administration at Day 1 and Day 90 300 mg subcutaneous administration at Day 1 and Day 90 Saline subcutaneous administration at Day 1 and Day 90
Period Title: Overall Study
Started 60 62 66 65 62 63 61 62
Treated 60 61 65 65 61 62 61 62
Completed [1] 59 59 58 60 57 59 57 60
Not Completed 1 3 8 5 5 4 4 2
[1]
LDL-C returned to >80% of baseline from Day 210-360 or completed Day 360 with LDL-C<=80% of baseline
Arm/Group Title Placebo (Single-dose) Inclisiran 200 mg (Single-dose) Inclisiran 300 mg (Single-dose) Inclisiran 500 mg (Single-dose) Placebo (Double-dose) Inclisiran 100 mg (Double-dose) Inclisiran 200 mg (Double-dose) Inclisiran 300 mg (Double-dose) Total
Hide Arm/Group Description Saline subcutaneous administration once at Day 1 200 mg subcutaneous administration once at Day 1 300 mg subcutaneous administration once at Day 1 500 mg subcutaneous administration once at Day 1 Saline subcutaneous administration at Day 1 and Day 90 100 mg subcutaneous administration at Day 1 and Day 90 200 mg subcutaneous administration at Day 1 and Day 90 300 mg subcutaneous administration at Day 1 and Day 90 Total of all reporting groups
Overall Number of Baseline Participants 65 60 62 66 62 62 63 61 501
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 60 participants 62 participants 66 participants 62 participants 62 participants 63 participants 61 participants 501 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
40
  61.5%
30
  50.0%
27
  43.5%
32
  48.5%
32
  51.6%
24
  38.7%
37
  58.7%
31
  50.8%
253
  50.5%
>=65 years
25
  38.5%
30
  50.0%
35
  56.5%
34
  51.5%
30
  48.4%
38
  61.3%
26
  41.3%
30
  49.2%
248
  49.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 65 participants 60 participants 62 participants 66 participants 62 participants 62 participants 63 participants 61 participants 501 participants
62.0  (11.4) 63.9  (10.8) 64.1  (12.8) 62.1  (12.4) 62.8  (10.3) 65.2  (9.4) 62.3  (10.8) 64.1  (9.4) 63.6  (10.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 60 participants 62 participants 66 participants 62 participants 62 participants 63 participants 61 participants 501 participants
Female
23
  35.4%
21
  35.0%
20
  32.3%
19
  28.8%
29
  46.8%
23
  37.1%
24
  38.1%
16
  26.2%
175
  34.9%
Male
42
  64.6%
39
  65.0%
42
  67.7%
47
  71.2%
33
  53.2%
39
  62.9%
39
  61.9%
45
  73.8%
326
  65.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 60 participants 62 participants 66 participants 62 participants 62 participants 63 participants 61 participants 501 participants
Hispanic or Latino
7
  10.8%
4
   6.7%
3
   4.8%
1
   1.5%
2
   3.2%
2
   3.2%
6
   9.5%
4
   6.6%
29
   5.8%
Not Hispanic or Latino
58
  89.2%
56
  93.3%
59
  95.2%
65
  98.5%
60
  96.8%
60
  96.8%
57
  90.5%
57
  93.4%
472
  94.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 60 participants 62 participants 66 participants 62 participants 62 participants 63 participants 61 participants 501 participants
American Indian or Alaska Native
1
   1.5%
0
   0.0%
1
   1.6%
1
   1.5%
0
   0.0%
2
   3.2%
0
   0.0%
1
   1.6%
6
   1.2%
Asian
0
   0.0%
2
   3.3%
2
   3.2%
2
   3.0%
1
   1.6%
1
   1.6%
0
   0.0%
1
   1.6%
9
   1.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
1
   1.6%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
Black or African American
4
   6.2%
4
   6.7%
2
   3.2%
0
   0.0%
3
   4.8%
2
   3.2%
2
   3.2%
1
   1.6%
18
   3.6%
White
59
  90.8%
53
  88.3%
56
  90.3%
63
  95.5%
58
  93.5%
57
  91.9%
61
  96.8%
58
  95.1%
465
  92.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   1.5%
1
   1.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   0.4%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 60 participants 62 participants 66 participants 62 participants 62 participants 63 participants 61 participants 501 participants
Canada 8 8 7 12 10 10 7 9 71
Netherlands 22 21 21 21 20 20 23 21 169
United States 12 10 10 12 8 10 12 10 84
United Kingdom 11 11 11 11 10 9 11 12 86
Germany 12 10 13 10 14 13 10 9 91
1.Primary Outcome
Title Percentage Change in LDL-C From Baseline to Day 180
Hide Description Percent Change in LDL-C (beta-quantification) from Baseline to Day 180 in MITT Population
Time Frame Baseline to 180 days
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (MITT) population
Arm/Group Title Placebo (Single Dose) 200 mg (Single Dose) 300 mg (Single Dose) 500 mg (Single Dose) Placebo (Double Dose) 100 mg (Double Dose) 200 mg (Double Dose) 300 mg (Double Dose)
Hide Arm/Group Description:
Saline via subcutaneous injection - Single Dose on Day 1
200 mg Inclisiran via subcutaneous injection - Single Dose on Day 1
300 mg Inclisiran via subcutaneous injection - Single Dose on Day 1
500 mg Inclisiran via subcutaneous injection - Single Dose on Day 1
Saline via subcutaneous injection - Two Doses: Day 1 and Day 90
100 mg Inclisiran via subcutaneous injection - Two Doses: Day 1 and Day 90
200 mg Inclisiran via subcutaneous injection - Two Doses: Day 1 and Day 90
300 mg Inclisiran via subcutaneous injection - Two Doses: Day 1 and Day 90
Overall Number of Participants Analyzed 64 60 60 60 61 59 60 59
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent change
2.1
(-2.9 to 7.2)
-27.9
(-33.1 to -22.7)
-38.4
(-43.6 to -33.2)
-41.9
(-47.2 to -36.7)
1.8
(-2.6 to 6.3)
-35.5
(-40.0 to -31.0)
-44.9
(-49.3 to -40.4)
-52.6
(-57.1 to -48.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Single Dose), 200 mg (Single Dose)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Two sample t-tests were performed to test the superiority of any dosing group over placebo. A Dunnett multiple t-test procedure was applied to adjust for multiple comparisons with six different dosing regimens.
Statistical Test of Hypothesis P-Value <0.0001
Comments This P-Value applies to the comparison of the mean percent change at Day 180 for the 200 mg (Single-Dose) Inclisiran group versus Placebo (Single-Dose).
Method t-test, 1 sided
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo (Single Dose), 300 mg (Single Dose)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Two sample t-tests were performed to test the superiority of any dosing group over placebo. A Dunnett multiple t-test procedure was applied to adjust for multiple comparisons with six different dosing regimens.
Statistical Test of Hypothesis P-Value <0.0001
Comments This P-Value applies to the comparison of the mean percent change at Day 180 for the 300 mg (Single-Dose) Inclisiran group versus Placebo (Single-Dose).
Method t-test, 1 sided
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo (Single Dose), 500 mg (Single Dose)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Two sample t-tests were performed to test the superiority of any dosing group over placebo. A Dunnett multiple t-test procedure was applied to adjust for multiple comparisons with six different dosing regimens.
Statistical Test of Hypothesis P-Value <0.0001
Comments This P-Value applies to the comparison of the mean percent change at Day 180 for the 500 mg (Single-Dose) Inclisiran group versus Placebo (Single-Dose).
Method t-test, 1 sided
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo (Double Dose), 100 mg (Double Dose)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Two sample t-tests were performed to test the superiority of any dosing group over placebo. A Dunnett multiple t-test procedure was applied to adjust for multiple comparisons with six different dosing regimens.
Statistical Test of Hypothesis P-Value <0.0001
Comments This P-Value applies to the comparison of the mean percent change at Day 180 for the 100 mg Double-Dose) Inclisiran group versus Placebo (Double-Dose).
Method t-test, 1 sided
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo (Double Dose), 200 mg (Double Dose)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Two sample t-tests were performed to test the superiority of any dosing group over placebo. A Dunnett multiple t-test procedure was applied to adjust for multiple comparisons with six different dosing regimens.
Statistical Test of Hypothesis P-Value <0.0001
Comments This P-Value applies to the comparison of the mean percent change at Day 180 for the 200 mg Double-Dose) Inclisiran group versus Placebo (Double-Dose).
Method t-test, 1 sided
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo (Double Dose), 300 mg (Double Dose)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Two sample t-tests were performed to test the superiority of any dosing group over placebo. A Dunnett multiple t-test procedure was applied to adjust for multiple comparisons with six different dosing regimens.
Statistical Test of Hypothesis P-Value <0.0001
Comments This P-Value applies to the comparison of the mean percent change at Day 180 for the 300 mg Double-Dose) Inclisiran group versus Placebo (Double-Dose).
Method t-test, 1 sided
Comments [Not Specified]
2.Secondary Outcome
Title Percentage Change in LDL-C From Baseline to Day 90
Hide Description Percent Change in LDL-C (beta-quantification) from Baseline to Day 90 in MITT Population
Time Frame Baseline to 90 days
Hide Outcome Measure Data
Hide Analysis Population Description
In this analysis, the single and double-dose 200mg arms were combined, as were the single and double-dose 300mg arms. The second dose for patients in double-dose arms was given on Day 90. Therefore, up to day 90, those patients in double-dose arms received the same treatment as patients in the single dose arms within the same dose amount.
Arm/Group Title Single Dose 500 mg Double Dose 100 mg Single and Double Dose Placebo Single and Double Dose 200 mg Single and Double Dose 300 mg
Hide Arm/Group Description:
500 mg subcutaneous injection - Single Dose on Day 1 (2 injections)
200 mg Inclisiran via subcutaneous injection - Two Doses (Day 1 and Day 90)
Saline: Single Dose (Day 1) or Two Doses (Day 1 and Day 90)
200 mg Inclisiran via subcutaneous injection: Single Dose (Day 1) or Two Doses (Day 1 and Day 90)
300 mg Inclisiran via subcutaneous injection: Single Dose (Day 1) or Two Doses (Day 1 and Day 90)
Overall Number of Participants Analyzed 60 59 125 120 118
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent change
-49
(-53.8 to -44.2)
-34.2
(-39.1 to -29.3)
-0.8
(-4.2 to 2.5)
-41.8
(-45.3 to -38.4)
-45.7
(-49.2 to -42.3)
3.Secondary Outcome
Title Percent Change From Baseline In LDL-C Levels At Day 60, Day 120, and Day 210
Hide Description This outcome measure evaluated the effects of both single- and double-dose inclisiran on LDL-C levels in the mITT population from baseline to Day 60, Day 120, and Day 210.
Time Frame Baseline, Day 60, Day 120, and Day 210
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo (Single Dose) Inclisiran 200 mg (Single Dose) Inclisiran 300 mg (Single Dose) Inclisiran 500 mg (Single Dose) Placebo (Double Dose) Inclisiran 100 mg (Double Dose) Inclisiran 200 mg (Double Dose) Inclisiran 300 mg (Double Dose)
Hide Arm/Group Description:
Saline subcutaneous administration once at Day 1
200 mg subcutaneous administration once at Day 1
300 mg subcutaneous administration once at Day 1
500 mg subcutaneous administration once at Day 1
Saline subcutaneous administration twice at Day 1 and Day 90
100 mg subcutaneous administration twice at Day 1 and Day 90
200 mg subcutaneous administration twice at Day 1 and Day 90
300 mg subcutaneous administration twice at Day 1 and Day 90
Overall Number of Participants Analyzed 64 60 60 60 61 59 60 59
Mean (95% Confidence Interval)
Unit of Measure: Percent change
Day 60
-4.27
(-7.84 to -0.7)
-44.32
(-50.55 to -38.09)
-50.87
(-55.62 to -46.12)
-49.58
(-54.12 to -45.04)
-1.92
(-6.7 to 2.85)
-35.73
(-40.23 to -31.23)
-44.28
(-49.1 to -39.47)
-50.99
(-55.51 to -45.67)
Day 120
-0.91
(-5.17 to 3.34)
-36.94
(-42.8 to -31.08)
-43.32
(-48.95 to -37.68)
-46.42
(-50.63 to -42.22)
0.17
(-3.61 to 3.95)
-41.37
(-45.94 to -36.8)
-49.54
(-54.6 to -44.49)
-54.73
(-59.88 to -49.58)
Day 210
1.45
(-3.61 to 6.06)
-28.98
(-36.83 to -21.12)
-35.39
(-41.47 to -29.31)
-39.2
(-43.71 to -34.68)
0.58
(-4.58 to 5.74)
-31.67
(-36.08 to -27.27)
-42.59
(-47.11 to -38.08)
-50.54
(-54.83 to -46.25)
4.Secondary Outcome
Title Number of Participants With an LDL-C Greater Than 80% of the Baseline Value at Day 180 and Day 210
Hide Description This outcome measure evaluated the number of participants (single and double dose) in the mITT population with an LDL-C greater than 80% of the baseline value at Day 180 and Day 210.
Time Frame Baseline, Day 180, Day 210
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo (Single-dose) Inclisiran 200 mg (Single-dose) Inclisiran 300 mg (Single-dose) Inclisiran 500 mg (Single-dose) Placebo (Double-dose) Inclisiran 100 mg (Double-dose) Inclisiran 200 mg (Double-dose) Inclisiran 300 mg (Double-dose)
Hide Arm/Group Description:
Saline subcutaneous administration once at Day 1
200 mg subcutaneous administration once at Day 1
300 mg subcutaneous administration once at Day 1
500 mg subcutaneous administration once at Day 1
Saline subcutaneous administration at Day 1 and Day 90
100 mg subcutaneous administration at Day 1 and Day 90
200 mg subcutaneous administration at Day 1 and Day 90
300 mg subcutaneous administration at Day 1 and Day 90
Overall Number of Participants Analyzed 64 60 60 60 61 59 60 59
Measure Type: Count of Participants
Unit of Measure: Participants
Day 180
35
  54.7%
6
  10.0%
5
   8.3%
0
   0.0%
29
  47.5%
2
   3.4%
1
   1.7%
0
   0.0%
Day 210
34
  53.1%
8
  13.3%
5
   8.3%
2
   3.3%
34
  55.7%
1
   1.7%
1
   1.7%
1
   1.7%
5.Secondary Outcome
Title Number of Participants With Individual Responsiveness as Measured By LDL-C Levels at Day 90 and Day 180
Hide Description This outcome measure evaluated the individual responsiveness of participants to inclisiran (single and double dose) in the mITT population as defined by an LDL-C level of <25 mg/deciliter [dL] at Day 90 and Day 180.
Time Frame Day 90, Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo (Single-dose) Inclisiran 200 mg (Single-dose) Inclisiran 300 mg (Single-dose) Inclisiran 500 mg (Single-dose) Placebo (Double-dose) Inclisiran 100 mg (Double-dose) Inclisiran 200 mg (Double-dose) Inclisiran 300 mg (Double-dose)
Hide Arm/Group Description:
Saline subcutaneous administration once at Day 1
200 mg subcutaneous administration once at Day 1
300 mg subcutaneous administration once at Day 1
500 mg subcutaneous administration once at Day 1
Saline subcutaneous administration at Day 1 and Day 90
100 mg subcutaneous administration at Day 1 and Day 90
200 mg subcutaneous administration at Day 1 and Day 90
300 mg subcutaneous administration at Day 1 and Day 90
Overall Number of Participants Analyzed 64 60 60 60 61 59 60 59
Measure Type: Count of Participants
Unit of Measure: Participants
Day 90
0
   0.0%
0
   0.0%
5
   8.3%
3
   5.0%
0
   0.0%
0
   0.0%
1
   1.7%
0
   0.0%
Day 180
0
   0.0%
0
   0.0%
1
   1.7%
2
   3.3%
0
   0.0%
1
   1.7%
2
   3.3%
3
   5.1%
6.Secondary Outcome
Title Number of Participants With Greater Or Equal To 50% LDL-C Reduction From Baseline At Day 180
Hide Description This outcome measure evaluated the number of participants (single and double dose) in the mITT population with an LDL-C reduction greater than 50% of the baseline value at Day 180.
Time Frame Baseline, Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo (Single-dose) Inclisiran 200 mg (Single-dose) Inclisiran 300 mg (Single-dose) Inclisiran 500 mg (Single-dose) Placebo (Double-dose) Inclisiran 100 mg (Double-dose) Inclisiran 200 mg (Double-dose) Inclisiran 300 mg (Double-dose)
Hide Arm/Group Description:
Saline subcutaneous administration once at Day 1
200 mg subcutaneous administration once at Day 1
300 mg subcutaneous administration once at Day 1
500 mg subcutaneous administration once at Day 1
Saline subcutaneous administration at Day 1 and Day 90
100 mg subcutaneous administration at Day 1 and Day 90
200 mg subcutaneous administration at Day 1 and Day 90
300 mg subcutaneous administration at Day 1 and Day 90
Overall Number of Participants Analyzed 64 60 60 60 61 59 60 59
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
9
  15.0%
19
  31.7%
16
  26.7%
0
   0.0%
14
  23.7%
27
  45.0%
32
  54.2%
7.Secondary Outcome
Title Percentage Change in PCSK9 Levels From Baseline at Day 180
Hide Description This outcome measure evaluated the percent change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline to Day 180 in participants (single and double dose) in the mITT population.
Time Frame Baseline, Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo (Single Dose) Inclisiran 200 mg (Single Dose) Inclisiran 300 mg (Single Dose) Inclisiran 500 mg (Single Dose) Placebo (Double Dose) Inclisiran 100 mg (Double Dose) Inclisiran 200 mg (Double Dose) Inclisiran 300 mg (Double Dose)
Hide Arm/Group Description:
Saline subcutaneous administration once at Day 1
200 mg subcutaneous administration once at Day 1
300 mg subcutaneous administration once at Day 1
500 mg subcutaneous administration once at Day 1
Saline subcutaneous administration twice at Day 1 and Day 90
100 mg subcutaneous administration twice at Day 1 and Day 90
200 mg subcutaneous administration twice at Day 1 and Day 90
300 mg subcutaneous administration twice at Day 1 and Day 90
Overall Number of Participants Analyzed 64 60 60 60 61 59 60 59
Mean (Standard Deviation)
Unit of Measure: percent change
2.2  (23.4) -47.9  (21) -56  (19.2) -59.3  (18) -1.2  (20.7) -53.2  (20.9) -66.2  (15.6) -69.1  (12.1)
8.Secondary Outcome
Title Percentage Change in Other Lipids and Apolipoproteins From Baseline to Day 180
Hide Description This outcome measure evaluated the percent change from baseline to Day 180 in cholesterol (total, high-density lipoprotein [HDL], non-HDL) and apolipoproteins (B, A1) in participants (single and double dose) in the mITT population.
Time Frame Baseline, Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo (Single Dose) Inclisiran 200 mg (Single Dose) Inclisiran 300 mg (Single Dose) Inclisiran 500 mg (Single Dose) Placebo (Double Dose) Inclisiran 100 mg (Double Dose) Inclisiran 200 mg (Double Dose) Inclisiran 300 mg (Double Dose)
Hide Arm/Group Description:
Saline subcutaneous administration once at Day 1
200 mg subcutaneous administration once at Day 1
300 mg subcutaneous administration once at Day 1
500 mg subcutaneous administration once at Day 1
Saline subcutaneous administration twice at Day 1 and Day 90
100 mg subcutaneous administration twice at Day 1 and Day 90
200 mg subcutaneous administration twice at Day 1 and Day 90
300 mg subcutaneous administration twice at Day 1 and Day 90
Overall Number of Participants Analyzed 64 60 60 60 61 59 60 59
Mean (Standard Deviation)
Unit of Measure: percent change
Total Cholesterol 1.8  (12.1) -17.6  (19) -23.7  (15.7) -26.6  (10.7) 0.7  (12.3) -22.4  (12.4) -26.8  (13) 33.2  (11.3)
Non-HDL Cholesterol 1.5  (16.7) -25.1  (26.3) -35.2  (20.2) -36.9  (14) 1.3  (16.9) -31.7  (15.1) -38.9  (16.8) -46  (14.6)
HDL Cholesterol 3.8  (15.6) 4.4  (14.8) 8.8  (11.1) 6.9  (14) 0.5  (12.5) 7.6  (12.2) 10.3  (15.3) 8.6  (14.9)
Apolipoprotein B 1.7  (14.7) -22.9  (21) -30.8  (18) -33.1  (12.7) 0.9  (13) -27.8  (13.4) -35  (15.8) -40.9  (14.8)
Apolipoprotein A1 3.6  (10.6) 2.9  (9.3) 3.8  (8.9) 4.1  (10.9) 0.8  (8.3) 5.5  (10.6) 8.6  (11.5) 6.2  (11.9)
9.Secondary Outcome
Title Number of Participants Who Attained Global Lipid Modification Targets for Level of Atherosclerotic Cardiovascular Disease Risk
Hide Description

This outcome measure evaluated the proportion of participants (single and double dose) in the mITT population who attained a global lipid modification target by baseline cardiovascular risk group, looking specifically at LDL-C levels (mg/dL) in the category of cardiovascular disease (CVD).

CVD was defined as a participant who had at least 1 of the following: prior myocardial infarction, prior percutaneous coronary intervention, prior coronary artery bypass graft, prior stroke, prior transient ischemic attack, peripheral artery disease.

Time Frame Baseline, Day 180
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo (Single-dose) Inclisiran 200 mg (Single-dose) Inclisiran 300 mg (Single-dose) Inclisiran 500 mg (Single-dose) Placebo (Double-dose) Inclisiran 100 mg (Double-dose) Inclisiran 200 mg (Double-dose) Inclisiran 300 mg (Double-dose)
Hide Arm/Group Description:
Saline subcutaneous administration once at Day 1
200 mg subcutaneous administration once at Day 1
300 mg subcutaneous administration once at Day 1
500 mg subcutaneous administration once at Day 1
Saline subcutaneous administration at Day 1 and Day 90
100 mg subcutaneous administration at Day 1 and Day 90
200 mg subcutaneous administration at Day 1 and Day 90
300 mg subcutaneous administration at Day 1 and Day 90
Overall Number of Participants Analyzed 64 60 60 60 61 59 60 59
Measure Type: Count of Participants
Unit of Measure: Participants
CVD
45
  70.3%
43
  71.7%
46
  76.7%
33
  55.0%
45
  73.8%
41
  69.5%
39
  65.0%
42
  71.2%
<70 mg/dL
0
   0.0%
16
  26.7%
27
  45.0%
18
  30.0%
1
   1.6%
24
  40.7%
27
  45.0%
33
  55.9%
10.Secondary Outcome
Title Percentage Change in Other Lipids and Inflammatory Markers From Baseline to Day 180
Hide Description This outcome measure evaluated the percent change from baseline to Day 180 in triglycerides, very-low-density lipoprotein (VLDL) cholesterol, lipoprotein(a), and high sensitivity C-reactive protein (hsCRP) in participants (single and double dose) in the mITT population.
Time Frame Baseline, Day 180
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo (Single Dose) Inclisiran 200 mg (Single Dose) Inclisiran 300 mg (Single Dose) Inclisiran 500 mg (Single Dose) Placebo (Double Dose) Inclisiran 100 mg (Double Dose) Inclisiran 200 mg (Double Dose) Inclisiran 300 mg (Double Dose)
Hide Arm/Group Description:
Saline subcutaneous administration once at Day 1
200 mg subcutaneous administration once at Day 1
300 mg subcutaneous administration once at Day 1
500 mg subcutaneous administration once at Day 1
Saline subcutaneous administration twice at Day 1 and Day 90
100 mg subcutaneous administration twice at Day 1 and Day 90
200 mg subcutaneous administration twice at Day 1 and Day 90
300 mg subcutaneous administration twice at Day 1 and Day 90
Overall Number of Participants Analyzed 64 60 60 60 61 59 60 59
Median (Inter-Quartile Range)
Unit of Measure: percent change
Triglycerides
6.4
(-15.9 to 21.9)
1.1
(-18.5 to 17.8)
-12.8
(-27.8 to 7.8)
-12.2
(-25.6 to 7.7)
-3
(-17.2 to 22.6)
-6.3
(-17.6 to 10.9)
0.7
(-22.4 to 11.3)
-14.2
(-26.4 to 5.4)
VLDL Cholesterol
2.4
(-30.7 to 30.5)
-11.6
(-35.8 to 23.3)
-23.8
(-43 to -6.4)
-14.6
(-34.8 to 3.5)
2.7
(-20 to 26.7)
-16.4
(-31.3 to 0)
-21.2
(-38.5 to 13.2)
-16
(-38.2 to 9.1)
Lipoprotein(a)
0.5
(-13.9 to 14.8)
-14.3
(-29.5 to -3.5)
-14.3
(-25.4 to -5.6)
-18.2
(-35 to 1.6)
0
(-10 to 12.4)
-14.9
(-26.2 to -1.9)
-17.3
(-31.9 to -7.7)
-25.6
(-38.5 to -15.2)
hsCRP
-5.3
(-40.8 to 28.4)
7.1
(-30.7 to 70.9)
-16.2
(-45.8 to 50)
-19.8
(-50 to 32.7)
-20
(-50 to 30)
-12.5
(-42.9 to 29.4)
-16.3
(-34.6 to 24.3)
-16.7
(-50.9 to 33.3)
Time Frame Treatment Emergent Adverse Events up to Day 360
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo (Single Dose) Inclisiran 200 mg (Single Dose) Inclisiran 300 mg (Single Dose) Inclisiran 500 mg (Single Dose) Placebo (Double Dose) Inclisiran 100 mg (Double Dose) Inclisiran 200 mg (Double Dose) Inclisiran 300 mg (Double Dose)
Hide Arm/Group Description Saline subcutaneous administration once at Day 1 200 mg subcutaneous administration once at Day 1 300 mg subcutaneous administration once at Day 1 500 mg subcutaneous administration once at Day 1 Saline subcutaneous administration twice at Day 1 and Day 90 100 mg subcutaneous administration twice at Day 1 and Day 90 200 mg subcutaneous administration twice at Day 1 and Day 90 300 mg subcutaneous administration twice at Day 1 and Day 90
All-Cause Mortality
Placebo (Single Dose) Inclisiran 200 mg (Single Dose) Inclisiran 300 mg (Single Dose) Inclisiran 500 mg (Single Dose) Placebo (Double Dose) Inclisiran 100 mg (Double Dose) Inclisiran 200 mg (Double Dose) Inclisiran 300 mg (Double Dose)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/65 (0.00%)   0/60 (0.00%)   0/61 (0.00%)   1/65 (1.54%)   0/62 (0.00%)   0/61 (0.00%)   1/62 (1.61%)   0/61 (0.00%) 
Hide Serious Adverse Events
Placebo (Single Dose) Inclisiran 200 mg (Single Dose) Inclisiran 300 mg (Single Dose) Inclisiran 500 mg (Single Dose) Placebo (Double Dose) Inclisiran 100 mg (Double Dose) Inclisiran 200 mg (Double Dose) Inclisiran 300 mg (Double Dose)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/65 (4.62%)   11/60 (18.33%)   11/61 (18.03%)   8/65 (12.31%)   7/62 (11.29%)   13/61 (21.31%)   8/62 (12.90%)   9/61 (14.75%) 
Blood and lymphatic system disorders                 
Anameia  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  1/65 (1.54%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Cardiac disorders                 
Angina pectoris  1  0/65 (0.00%)  1/60 (1.67%)  1/61 (1.64%)  1/65 (1.54%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Angina unstable  1  1/65 (1.54%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Atrial flutter  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  1/65 (1.54%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Acute myocardial infarction  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  1/61 (1.64%)  0/62 (0.00%)  1/61 (1.64%) 
Atrial fibrillation  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Atrial tachycardia  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  1/61 (1.64%)  1/62 (1.61%)  0/61 (0.00%) 
Atriventricular block complete  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  1/62 (1.61%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Cardiac arrest  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  1/65 (1.54%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Coronary artery disease  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  2/61 (3.28%) 
Myocardial infarction  1  0/65 (0.00%)  1/60 (1.67%)  0/61 (0.00%)  2/65 (3.08%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Pericarditis  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  1/65 (1.54%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Ventricular extrasystoles  1  1/65 (1.54%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Gastrointestinal disorders                 
Aorta-oesophageal fistula  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Constipation  1  0/65 (0.00%)  0/60 (0.00%)  1/61 (1.64%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Gastritis  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Inguinal hernia  1  0/65 (0.00%)  1/60 (1.67%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
large instestine polyp  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  1/61 (1.64%)  0/62 (0.00%)  0/61 (0.00%) 
Proctitis ulcerative  1  0/65 (0.00%)  0/60 (0.00%)  1/61 (1.64%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Rectal haemorrhage  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  1/62 (1.61%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Volvulus  1  0/65 (0.00%)  1/60 (1.67%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Vomiting  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  1/65 (1.54%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
General disorders                 
Device dislocation  1  0/65 (0.00%)  0/60 (0.00%)  1/61 (1.64%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Non-cardiac chest pain  1  0/65 (0.00%)  0/60 (0.00%)  1/61 (1.64%)  0/65 (0.00%)  0/62 (0.00%)  1/61 (1.64%)  0/62 (0.00%)  0/61 (0.00%) 
Pain  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  1/65 (1.54%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Srent-graft endoleak  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Vascular stent restenosis  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  1/61 (1.64%)  0/62 (0.00%)  0/61 (0.00%) 
Hepatobiliary disorders                 
Hepatic haemorrhage  1  0/65 (0.00%)  0/60 (0.00%)  1/61 (1.64%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Infections and infestations                 
Appendicitis  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  1/61 (1.64%)  0/62 (0.00%)  0/61 (0.00%) 
Device related infection  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Erysipelas  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  1/62 (1.61%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Gastroenteritis  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  1/61 (1.64%)  0/62 (0.00%)  0/61 (0.00%) 
Implant site infection  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  1/61 (1.64%)  0/62 (0.00%)  0/61 (0.00%) 
Listeria sepsis  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Osteomyelitis  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  1/61 (1.64%)  0/62 (0.00%)  0/61 (0.00%) 
Urinary tract infection  1  0/65 (0.00%)  0/60 (0.00%)  1/61 (1.64%)  0/65 (0.00%)  1/62 (1.61%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Urosepsis  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Wound abcess  1  0/65 (0.00%)  0/60 (0.00%)  1/61 (1.64%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Injury, poisoning and procedural complications                 
Concussion  1  1/65 (1.54%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Facial bones fracture  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  1/61 (1.64%)  0/62 (0.00%)  0/61 (0.00%) 
Humerus fracture  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  1/61 (1.64%)  0/62 (0.00%)  0/61 (0.00%) 
Intentional overdose  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  1/62 (1.61%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Ligament sprain  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Limb crushing injury  1  0/65 (0.00%)  1/60 (1.67%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Multiple injuries  1  0/65 (0.00%)  0/60 (0.00%)  1/61 (1.64%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Pneumothorax traumatic  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  1/65 (1.54%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Post procedural complication  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  1/65 (1.54%)  0/62 (0.00%)  0/61 (0.00%)  2/62 (3.23%)  0/61 (0.00%) 
Post procedural haemorrhage  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  1/65 (1.54%)  1/62 (1.61%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Thoracic vertebral fracture  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  1/65 (1.54%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Traumatic haemothorax  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  1/65 (1.54%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Upperlimb fracture  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  1/65 (1.54%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Weaning failure  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Investigations                 
Haemoglobin decreased  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  1/62 (1.61%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Platelet count decreased  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  1/62 (1.61%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Transaminases increased  1  0/65 (0.00%)  0/60 (0.00%)  1/61 (1.64%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Metabolism and nutrition disorders                 
Dehydration  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Hypoglycemia  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  1/61 (1.64%)  0/62 (0.00%)  0/61 (0.00%) 
Musculoskeletal and connective tissue disorders                 
Muscle necrosis  1  1/65 (1.54%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Osteitis  1  0/65 (0.00%)  1/60 (1.67%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Osteoarthritis  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  1/61 (1.64%)  0/62 (0.00%)  0/61 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Adeoncarcinoma of colon  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Bladder cancer  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Bladder transitional cell carcinoma stage 0  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Gastrointestinal tract adenoma  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Glioblastoma  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Hepatocellular carcinoma  1  0/65 (0.00%)  0/60 (0.00%)  1/61 (1.64%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Intestinal adenocarcinoma  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
Non-small cell lung cancer stage 1  1  0/65 (0.00%)  0/60 (0.00%)  1/61 (1.64%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Oesophageal adenocarcinoma  1  0/65 (0.00%)  1/60 (1.67%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Pituitary tumour benign  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  1/65 (1.54%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Prostate cancer  1  0/65 (0.00%)  2/60 (3.33%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Squamous cell carcinoma of lung  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  1/65 (1.54%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Squamous cell carcinoma of skin  1  0/65 (0.00%)  1/60 (1.67%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Tongue neoplasm malignant  1  0/65 (0.00%)  1/60 (1.67%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Nervous system disorders                 
Carpal tunnel syndrome  1  0/65 (0.00%)  1/60 (1.67%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Ischaemic stroke  1  0/65 (0.00%)  0/60 (0.00%)  1/61 (1.64%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Lacunar stroke  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  1/61 (1.64%)  0/62 (0.00%)  0/61 (0.00%) 
Neuropathy peripheral  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  1/61 (1.64%)  0/62 (0.00%)  0/61 (0.00%) 
Spinal cord ischaemia  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Syncope  1  0/65 (0.00%)  1/60 (1.67%)  1/61 (1.64%)  0/65 (0.00%)  1/62 (1.61%)  0/61 (0.00%)  1/62 (1.61%)  1/61 (1.64%) 
Renal and urinary disorders                 
Acute kidney injury  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Calculus urinary  1  0/65 (0.00%)  1/60 (1.67%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Stress urinary incontinence  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  1/62 (1.61%)  0/61 (0.00%)  0/62 (0.00%)  0/61 (0.00%) 
Respiratory, thoracic and mediastinal disorders                 
Chronic obstructive pulmonary disease  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Vascular disorders                 
Aortic dissection  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Hypotension  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  1/61 (1.64%)  0/62 (0.00%)  0/61 (0.00%) 
Intermittent claudication  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Orthostatic hypotension  1  0/65 (0.00%)  0/60 (0.00%)  0/61 (0.00%)  0/65 (0.00%)  0/62 (0.00%)  0/61 (0.00%)  0/62 (0.00%)  1/61 (1.64%) 
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo (Single Dose) Inclisiran 200 mg (Single Dose) Inclisiran 300 mg (Single Dose) Inclisiran 500 mg (Single Dose) Placebo (Double Dose) Inclisiran 100 mg (Double Dose) Inclisiran 200 mg (Double Dose) Inclisiran 300 mg (Double Dose)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   50/65 (76.92%)   49/60 (81.67%)   49/61 (80.33%)   54/65 (83.08%)   51/62 (82.26%)   47/61 (77.05%)   49/62 (79.03%)   51/61 (83.61%) 
Cardiac disorders                 
Angina pectoris  1  1/65 (1.54%)  2/60 (3.33%)  4/61 (6.56%)  1/65 (1.54%)  2/62 (3.23%)  0/61 (0.00%)  2/62 (3.23%)  0/61 (0.00%) 
Gastrointestinal disorders                 
Abdominal pain  1  2/65 (3.08%)  3/60 (5.00%)  2/61 (3.28%)  0/65 (0.00%)  3/62 (4.84%)  2/61 (3.28%)  1/62 (1.61%)  4/61 (6.56%) 
Constipation  1  1/65 (1.54%)  4/60 (6.67%)  2/61 (3.28%)  1/65 (1.54%)  2/62 (3.23%)  0/61 (0.00%)  2/62 (3.23%)  1/61 (1.64%) 
Diarrhoea  1  1/65 (1.54%)  1/60 (1.67%)  4/61 (6.56%)  4/65 (6.15%)  2/62 (3.23%)  3/61 (4.92%)  7/62 (11.29%)  5/61 (8.20%) 
Nausea  1  2/65 (3.08%)  1/60 (1.67%)  1/61 (1.64%)  4/65 (6.15%)  3/62 (4.84%)  2/61 (3.28%)  4/62 (6.45%)  3/61 (4.92%) 
Vomiting  1  0/65 (0.00%)  1/60 (1.67%)  2/61 (3.28%)  1/65 (1.54%)  0/62 (0.00%)  0/61 (0.00%)  4/62 (6.45%)  0/61 (0.00%) 
General disorders                 
Fatigue  1  5/65 (7.69%)  2/60 (3.33%)  4/61 (6.56%)  2/65 (3.08%)  6/62 (9.68%)  2/61 (3.28%)  0/62 (0.00%)  1/61 (1.64%) 
Infections and infestations                 
Gastroenteritis  1  0/65 (0.00%)  3/60 (5.00%)  2/61 (3.28%)  1/65 (1.54%)  2/62 (3.23%)  3/61 (4.92%)  1/62 (1.61%)  1/61 (1.64%) 
Influenza  1  3/65 (4.62%)  3/60 (5.00%)  4/61 (6.56%)  5/65 (7.69%)  2/62 (3.23%)  3/61 (4.92%)  4/62 (6.45%)  5/61 (8.20%) 
Nasopharyngitis  1  4/65 (6.15%)  8/60 (13.33%)  9/61 (14.75%)  9/65 (13.85%)  8/62 (12.90%)  8/61 (13.11%)  5/62 (8.06%)  11/61 (18.03%) 
Upper respiratory tract infection  1  2/65 (3.08%)  2/60 (3.33%)  4/61 (6.56%)  5/65 (7.69%)  2/62 (3.23%)  2/61 (3.28%)  1/62 (1.61%)  3/61 (4.92%) 
Urinary tract infection  1  1/65 (1.54%)  1/60 (1.67%)  5/61 (8.20%)  0/65 (0.00%)  4/62 (6.45%)  1/61 (1.64%)  1/62 (1.61%)  2/61 (3.28%) 
Injury, poisoning and procedural complications                 
Contusion  1  1/65 (1.54%)  1/60 (1.67%)  2/61 (3.28%)  2/65 (3.08%)  5/62 (8.06%)  3/61 (4.92%)  1/62 (1.61%)  2/61 (3.28%) 
Fall  1  1/65 (1.54%)  0/60 (0.00%)  1/61 (1.64%)  1/65 (1.54%)  1/62 (1.61%)  4/61 (6.56%)  1/62 (1.61%)  0/61 (0.00%) 
Investigations                 
Blood creatine phosphokinase increased  1  3/65 (4.62%)  1/60 (1.67%)  1/61 (1.64%)  0/65 (0.00%)  5/62 (8.06%)  0/61 (0.00%)  3/62 (4.84%)  0/61 (0.00%) 
Musculoskeletal and connective tissue disorders                 
Arthralgia  1  2/65 (3.08%)  4/60 (6.67%)  4/61 (6.56%)  4/65 (6.15%)  1/62 (1.61%)  2/61 (3.28%)  5/62 (8.06%)  3/61 (4.92%) 
Back pain  1  5/65 (7.69%)  4/60 (6.67%)  4/61 (6.56%)  4/65 (6.15%)  2/62 (3.23%)  6/61 (9.84%)  1/62 (1.61%)  4/61 (6.56%) 
Musculoskeletal pain  1  1/65 (1.54%)  2/60 (3.33%)  0/61 (0.00%)  1/65 (1.54%)  4/62 (6.45%)  0/61 (0.00%)  0/62 (0.00%)  6/61 (9.84%) 
Myalgia  1  3/65 (4.62%)  2/60 (3.33%)  6/61 (9.84%)  3/65 (4.62%)  3/62 (4.84%)  7/61 (11.48%)  5/62 (8.06%)  5/61 (8.20%) 
Pain in extremity  1  2/65 (3.08%)  2/60 (3.33%)  1/61 (1.64%)  2/65 (3.08%)  4/62 (6.45%)  1/61 (1.64%)  4/62 (6.45%)  1/61 (1.64%) 
Nervous system disorders                 
Dizziness  1  3/65 (4.62%)  1/60 (1.67%)  2/61 (3.28%)  2/65 (3.08%)  6/62 (9.68%)  3/61 (4.92%)  3/62 (4.84%)  3/61 (4.92%) 
Headache  1  6/65 (9.23%)  2/60 (3.33%)  2/61 (3.28%)  2/65 (3.08%)  5/62 (8.06%)  5/61 (8.20%)  1/62 (1.61%)  5/61 (8.20%) 
Respiratory, thoracic and mediastinal disorders                 
Cough  1  2/65 (3.08%)  4/60 (6.67%)  7/61 (11.48%)  3/65 (4.62%)  3/62 (4.84%)  1/61 (1.64%)  6/62 (9.68%)  3/61 (4.92%) 
Epistaxis  1  4/65 (6.15%)  0/60 (0.00%)  0/61 (0.00%)  1/65 (1.54%)  1/62 (1.61%)  0/61 (0.00%)  1/62 (1.61%)  0/61 (0.00%) 
Vascular disorders                 
Hypertension  1  0/65 (0.00%)  2/60 (3.33%)  3/61 (4.92%)  1/65 (1.54%)  3/62 (4.84%)  4/61 (6.56%)  2/62 (3.23%)  1/61 (1.64%) 
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The only disclosure restriction on the PI is that Sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period of more than 60 days but less than/equal to 180 days from the time submitted to Sponsor for review, allowing Sponsor to file a patent application or take such other measures as Sponsor deems appropriate to establish and preserve its proprietary rights. Sponsor may remove confidential or proprietary information.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Health Science Center
Organization: The Medicine's Company
Phone: 1-888-997-6326
EMail: Medical.Information@themedco.com
Publications:
ALN TTRSC-001; EudraCT 2012 004203 12
ALN-TTRSC-002; EudraCT 2013 002856 33
Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC Jr, Tomaselli GF; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S1-45. doi: 10.1161/01.cir.0000437738.63853.7a. Epub 2013 Nov 12. Erratum in: Circulation. 2014 Jun 24;129(25 Suppl 2):S46-8. Erratum in: Circulation. 2015 Dec 22;132(25):e396.
World Health Organization Cardiovascular Statistics, 2011, http://www.who.int/mediacentre/factsheets/fs317/en/index.html
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT02597127    
Other Study ID Numbers: MDCO-PCS-15-01
First Submitted: November 3, 2015
First Posted: November 5, 2015
Results First Submitted: February 4, 2019
Results First Posted: May 17, 2019
Last Update Posted: May 17, 2019