ORION-1: Trial to Evaluate the Effect of ALN-PCSSC Treatment on Low Density Lipoprotein Cholesterol (LDL-C)
Sponsor
The Medicines Company (Industry)
Overall Status
Completed
CT.gov ID
NCT02597127
Collaborator
(none)
501
54
8
17.2
9.3
0.5
Study Details
Study Description
Brief Summary
This study is a Phase II, placebo-controlled, double-blind, randomized trial in 480 participants with atherosclerotic cardiovascular disease (ASCVD) or ASCVD-risk equivalents (for example, diabetes and familial hypercholesterolemia) and elevated LDL-C despite maximum tolerated dose of LDL-C lowering therapies to evaluate the efficacy, safety, and tolerability of ALN-PCSSC injection(s).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Participants will be screened and 480 eligible participants will be randomized: 60 participants per each of six ALN-PCSSC dose groups plus 120 participants total across the placebo groups (20 participants each to match each of the six drug dose groups). Treatment allocation will be stratified by country and by current use of statins or other lipid-modifying therapies. Each participant will receive either one or two injections on Day 1 or a single injection on Day 1 and on Day 90 of blinded ALN-PCSSC or placebo.
Formation of anti-drug antibodies (ADA) will be assessed on Day 1 (prior to and 4 hours after the injection) and on Days 30, 60, 90, 120, 150, 180 (Days 150 and 180 only in participants who receive a second dose of study drug), and 210 or until any ADA response becomes negative within the study duration.
The independent Data Monitoring Committee (DMC) will review safety data beginning after the first 40 participants receive the first injection of ALN-PCSSC or placebo and complete the Day 14 follow-up visit. Thereafter, the DMC will review safety data every 2 months until the end of the trial. A recommendation may be taken to stop or amend the study at any of these reviews.
On Day 1, all eligible participants will be randomized and receive the first subcutaneous (SC) administration of ALN-PCSSC or placebo. After the first study drug administration, the participant will be observed in the clinic for at least 4 hours post injection before being discharged. Participants will return at Day 14 and then at monthly intervals for 6 months. Participants randomized to receive a second dose of study drug will receive the second injection of ALN-PCSSC or placebo at the Day 90 visit.
Efficacy assessments will include the measurement of the effects of ALN-PCSSC on levels of LDL-C lipids and lipoproteins including total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, very low-density lipoprotein (VLDL), apolipoprotein A1 (Apo-AI), apolipoprotein B (Apo-B), lipoprotein (a) [Lp(a)], C-reactive protein (CRP), and proprotein convertase subtilisin/kexin type 9 (PCSK9).
End of study (EOS) evaluations will be conducted at the EOS visit (Day 210). The expected duration of the participants' involvement in the study will be approximately 374 days, which includes screening, study drug administration, the course of single or multiple injections, and the follow-up period to Day 360.
Participants completing the study to Day 210 will be given the opportunity to enroll in a separate long-term extension study. Any participants in whom LDL-C levels have not returned to >80% of baseline values will continue to be followed as part of this study until either this level has been reached or until a maximum of Day 360, at which point they will be given the opportunity to enroll in the long-term extension study. At each visit, LDL-C levels, adverse events, serious adverse events, concomitant medications, and safety laboratory assessments will be collected.
Objectives:
Primary:
To evaluate the effect of ALN-PCSSC treatment on LDL-C levels at Day 180.
Secondary:
To evaluate the effect of ALN-PCSSC on the following:
-
LDL-C at Day 90
-
LDL-C levels at other time points
-
PCSK9 levels over time
-
Other lipids, lipoproteins, apolipoproteins
-
Proportion of participants achieving pre-specified global lipid guidelines
-
Individual responsiveness to different doses
-
Duration of lipid-lowering effect of different doses
-
Safety and tolerability profile of ALN-PCSSC
Exploratory:
To collect/evaluate the effect of ALN-PCSSC on the following:
-
Cardiovascular (CV) events such as CV death, non-fatal myocardial infarction, resuscitated cardiac arrest and non-fatal stroke (ischemic and hemorrhagic)
-
Evaluation of ADA for the investigational product
Study Design
Study Type:
Interventional
Actual Enrollment
:
501 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Placebo-controlled, Double-blind, Randomized Trial to Compare the Effect of Different Doses of ALN-PCSSC Given as Single or Multiple Subcutaneous Injections in Subjects With High Cardiovascular Risk and Elevated LDL-C
Study Start Date
:
Jan 1, 2016
Actual Primary Completion Date
:
Jun 7, 2017
Actual Study Completion Date
:
Jun 7, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ALN-PCSSC 200 mg (bi-annual dosing) ALN-PCSSC 200 milligram (mg) SC administration once at Day 1 |
Drug: ALN-PCSSC
ALN-PCSSC is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis and is given as SC injections
Other Names:
|
| Experimental: ALN-PCSSC 300 mg (bi-annual dosing) ALN-PCSSC 300 mg SC administration once at Day 1 |
Drug: ALN-PCSSC
ALN-PCSSC is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis and is given as SC injections
Other Names:
|
| Experimental: ALN-PCSSC 500 mg (bi-annual dosing) ALN-PCSSC 500 mg SC administration once at Day 1 |
Drug: ALN-PCSSC
ALN-PCSSC is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis and is given as SC injections
Other Names:
|
| Placebo Comparator: Normal Saline (bi-annual dosing) Saline SC administration once at Day 1 |
Drug: Normal Saline
Saline (sterile, normal, 0.9%) solution given as SC injections
|
| Experimental: ALN-PCSSC 100 mg (quarterly dosing) ALN-PCSSC 100 mg SC administration twice at Day 1 and Day 90 |
Drug: ALN-PCSSC
ALN-PCSSC is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis and is given as SC injections
Other Names:
|
| Experimental: ALN-PCSSC 200 mg (quarterly dosing) ALN-PCSSC 200 mg SC administration twice at Day 1 and Day 90 |
Drug: ALN-PCSSC
ALN-PCSSC is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis and is given as SC injections
Other Names:
|
| Experimental: ALN-PCSSC 300 mg (quarterly dosing) ALN-PCSSC 300 mg SC administration twice at Day 1 and Day 90 |
Drug: ALN-PCSSC
ALN-PCSSC is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis and is given as SC injections
Other Names:
|
| Placebo Comparator: Normal Saline (quarterly dosing) Saline SC administration twice at Day 1 and Day 90 |
Drug: Normal Saline
Saline (sterile, normal, 0.9%) solution given as SC injections
|
Outcome Measures
Primary Outcome Measures
- Percentage Change in LDL-C From Baseline to Day 180 [Baseline to 180 days]
Percent Change in LDL-C (beta-quantification) from Baseline to Day 180 in MITT Population
Secondary Outcome Measures
- Percentage Change in LDL-C From Baseline to Day 90 [Baseline to 90 days]
Percent Change in LDL-C (beta-quantification) from Baseline to Day 90 in MITT Population
- Percent Change From Baseline In LDL-C Levels At Day 60, Day 120, and Day 210 [Baseline, Day 60, Day 120, and Day 210]
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.
- Number of Participants With an LDL-C Greater Than 80% of the Baseline Value at Day 180 and Day 210 [Baseline, Day 180, Day 210]
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.
- Number of Participants With Individual Responsiveness as Measured By LDL-C Levels at Day 90 and Day 180 [Day 90, Day 180]
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.
- Number of Participants With Greater Or Equal To 50% LDL-C Reduction From Baseline At Day 180 [Baseline, Day 180]
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.
- Percentage Change in PCSK9 Levels From Baseline at Day 180 [Baseline, Day 180]
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.
- Percentage Change in Other Lipids and Apolipoproteins From Baseline to Day 180 [Baseline, Day 180]
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.
- Number of Participants Who Attained Global Lipid Modification Targets for Level of Atherosclerotic Cardiovascular Disease Risk [Baseline, Day 180]
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.
- Percentage Change in Other Lipids and Inflammatory Markers From Baseline to Day 180 [Baseline, Day 180]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 99 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male or female participants ≥18 years of age.
-
History of ASCVD or ASCVD-risk equivalents (symptomatic atherosclerosis, Type 2 diabetes, familial hypercholesterolemia, including participants whose 10-year risk of a CV event assessed by Framingham Risk Score (Framingham Risk Score >20%) or equivalent has a target LDL-C of <100 mg/deciliter [dL]).
-
Serum LDL-C ≥1.8 millimole (mmol)/liter (L) (≥70 mg/dL) for ASCVD participants or ≥2.6 mmol/L (≥100 mg/dL) for ASCVD-risk equivalent participants at screening.
-
Fasting triglyceride <4.52 mmol/L (<400 mg/dL) at screening.
-
Calculated glomerular filtration rate 30 mL/min or higher by estimated glomerular filtration rate (eGFR) using standardized local clinical methodology.
-
Participants on statins should be receiving a maximally tolerated dose (investigator's discretion).
-
Participants on lipid-lower therapies (such as statin and/or ezetimibe) should be on a stable dose for ≥30 days before screening with no planned medication or dose change during study participation.
-
Willing and able to give informed consent before initiation of any study-related procedures and willing to comply with all required study procedures.
Exclusion Criteria:
-
Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with participation in the clinical study, and/or put the participant at significant risk (according to investigator's [or delegate] judgment) if he/she participates in the clinical study.
-
An underlying known disease, or surgical, physical, or medical condition that, in the opinion of the investigator (or delegate), might interfere with interpretation of the clinical study results.
-
New York Heart Association (NYHA) class II, III, or IV heart failure or last known left ventricular ejection fraction <30%.
-
Cardiac arrhythmia within 3 months prior to randomization that is not controlled by medication or via ablation.
-
Any history of hemorrhagic stroke.
-
Major adverse cardiac event within 6 months prior to randomization.
-
Uncontrolled severe hypertension: systolic blood pressure >180 millimeters of mercury (mmHg) or diastolic blood pressure >110 mmHg prior to randomization despite anti-hypertensive therapy.
-
Poorly controlled Type 2 diabetes, such as, glycated hemoglobin A1c (HbA1c)>10.0% prior to randomization.
-
Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation >2x the upper limit of normal (ULN), or total bilirubin elevation >1.5x ULN at screening confirmed by a repeat measurement at least 1 week apart.
-
Serious comorbid disease in which the life expectancy of the participant is shorter than the duration of the trial (for example, acute systemic infection, cancer, or other serious illnesses). This includes all cancers with the exception of treated basal-cell carcinoma occurring >5 years before screening.
-
Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least two methods of contraception (oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, intrauterine device or tubal litigation) for the entire duration of the study. Women who are >2 years postmenopausal defined as ≥1 year since last menstrual period and if less than 55 years old with a negative pregnancy test within 24 hours of randomization or surgically sterile are exempt from this exclusion.
-
Males who are unwilling to use an acceptable method of birth control during the entire study period (such as, condom with spermicide).
-
Known history of alcohol and/or drug abuse within the last 5 years.
-
Treatment with other investigational medicinal products or devices within 30 days or five half˗lives, whichever is longer.
-
Use of other investigational medicinal products or devices during the course of the study.
-
Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to the following:
-
Inappropriate for this study, including participants who are unable to communicate or to cooperate with the investigator.
-
Unable to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study (including participants whose cooperation is doubtful due to drug abuse or alcohol dependency).
-
Unlikely to comply with the protocol requirements, instructions, and study-related restrictions (for example, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study).
-
Have any medical or surgical condition, which in the opinion of the investigator would put the participants at increased risk from participating in the study.
-
Involved with, or a relative of, someone directly involved in the conduct of the study.
-
Any known cognitive impairment (for example, Alzheimer's disease)
- Previous or current treatment (within 90 days of screening) with monoclonal antibodies directed at PCSK9.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Jacksonville Center for Clinical Research | Jacksonville | Florida | United States | 32216 |
| 2 | Midwest Institute For Clinical Research | Indianapolis | Indiana | United States | 46260 |
| 3 | Mount Sinai Icahn School of Medicine | New York | New York | United States | 10029 |
| 4 | Metabolic And Atherosclerosis Research Center | Cincinnati | Ohio | United States | 45227 |
| 5 | Sterling Research Group | Cincinnati | Ohio | United States | 45246 |
| 6 | Wellmont CVA Heart Institute | Greeneville | Tennessee | United States | 37745 |
| 7 | Amarillo Heart Clinical Research Institute, Inc. | Amarillo | Texas | United States | 79106 |
| 8 | National Clinical Research, Inc. | Richmond | Virginia | United States | 23294 |
| 9 | St. Paul's Hospital | Vancouver | British Columbia | Canada | V6Z 1Y6 |
| 10 | St. Boniface Hospital | Winnipeg | Manitoba | Canada | R2H 2A6 |
| 11 | Eastern Regional Health Authority, Patient Research Centre | St. Johns | Newfoundland and Labrador | Canada | A1B 3V6 |
| 12 | Brampton Research Associates | Brampton | Ontario | Canada | L6Z 4N5 |
| 13 | Lawson Health Research Institute | London | Ontario | Canada | N6C 2R5 |
| 14 | St. Michael's Hospital | Toronto | Ontario | Canada | M5C 2T2 |
| 15 | ECOGENE-21 Clinical Trials Center | Chicoutimi | Quebec | Canada | G7H 7K9 |
| 16 | Clinic Sante Cardio MC | Montreal | Quebec | Canada | H1T 3Y7 |
| 17 | Institut de Recherches Cliniques de Montreal | Montreal | Quebec | Canada | H2W 1R7 |
| 18 | Université Laval Quebec | Quebec City | Quebec | Canada | G1V 4G5 |
| 19 | Clinique des maladies lipidique Quebec | Quebec City | Quebec | Canada | G1V 4W2 |
| 20 | Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre hospitalier universitaire de Sherbrooke (CIUSSS de l'Estrie - CHUS) | Sherbrooke | Quebec | Canada | J1H 5N4 |
| 21 | Medical University Berlin | Berlin | Germany | 12203 | |
| 22 | Medical Center Essen | Essen | Germany | 45355 | |
| 23 | University Hospital Frankfurt | Frankfurt | Germany | 60590 | |
| 24 | University Heart Center Hamburg | Hamburg | Germany | 20251 | |
| 25 | Medical University Hospital Heidelberg, Internal medicine III | Heidelberg | Germany | 69120 | |
| 26 | Technical University Munich, German Heart Center | Munich | Germany | 80636 | |
| 27 | Amsterdam Medical Center | Amsterdam | Netherlands | 1105 AZ | |
| 28 | Haga Hospital | Den Haag | Netherlands | 2545 CH | |
| 29 | Deventer Ziekenhuis | Deventer | Netherlands | 7416 SE | |
| 30 | Andromed Eindhoven | Eindhoven | Netherlands | 5611 NV | |
| 31 | Admiraal de Ruyter Hospital, Cardiology | Goes | Netherlands | 4462 RA | |
| 32 | Bethesda Diabetes Research Center | Hoogeveen | Netherlands | 7909 AA | |
| 33 | Medisch Centrum Gorecht | Hoogezand | Netherlands | 9603 AE | |
| 34 | VOC Hoorn | Hoorn | Netherlands | 0031229284320 | |
| 35 | Leids Universitair Medisch Centrum (LUMC) | Leiden | Netherlands | 2333 ZA | |
| 36 | Andromed Rotterdam | Rotterdam | Netherlands | 3021 HC | |
| 37 | Diakonessenhuis, Vascular Policlinic | Utrecht | Netherlands | 3582 KE | |
| 38 | UMC Utrecht | Utrecht | Netherlands | 3584 CX | |
| 39 | VieCurie Venlo, Cardiology | Venlo | Netherlands | 5912 BL | |
| 40 | Albert Schweitzer Hospital, Cardiology | Zwijndrecht | Netherlands | 3331 LZ | |
| 41 | Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust | Birmingham | United Kingdom | B15 2TH | |
| 42 | Edinburgh Royal Infirmary | Edinburgh | United Kingdom | EH16 4SA | |
| 43 | The Royal Devon and Exeter NHS Trust | Exeter | United Kingdom | EX2 5DW | |
| 44 | Fowey River Practice | Fowey | United Kingdom | PL23 1DT | |
| 45 | Buckinghamshire NHS Trust | High Wycombe | United Kingdom | HP11 2TT | |
| 46 | Oak Tree Surgery | Liskeard | United Kingdom | Oak Tree Surgery | |
| 47 | Royal Free Hospital | London | United Kingdom | NW3 2QG | |
| 48 | Central Manchester University Hospital NHS Foundation Trust | Manchester | United Kingdom | M13 9WL | |
| 49 | The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital | Newcastle upon Tyne | United Kingdom | NE1 4LP | |
| 50 | The Alverton Practice | Penzance | United Kingdom | TR18 4JH | |
| 51 | Knowle House Surgery | Plymouth | United Kingdom | PL5 3JB | |
| 52 | Brannel Surgery | St. Austell | United Kingdom | St. Austell | |
| 53 | Rame Medical Ltd (Rame Research) | Torpoint | United Kingdom | PL11 2TB | |
| 54 | Worcestershire Acute NHS Trust | Worcester | United Kingdom | WR5 1DD |
Sponsors and Collaborators
- The Medicines Company
Investigators
- Principal Investigator: Kausik K Ray, MD, Department of Public Health and Primary Care, Imperial College London, Reynolds Building
Study Documents (Full-Text)
More Information
Publications
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- Stein EA, Mellis S, Yancopoulos GD, Stahl N, Logan D, Smith WB, Lisbon E, Gutierrez M, Webb C, Wu R, Du Y, Kranz T, Gasparino E, Swergold GD. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med. 2012 Mar 22;366(12):1108-18. doi: 10.1056/NEJMoa1105803.
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Responsible Party:
The Medicines Company
ClinicalTrials.gov Identifier:
NCT02597127
Other Study ID Numbers:
- MDCO-PCS-15-01
First Posted:
Nov 5, 2015
Last Update Posted:
May 17, 2019
Last Verified:
Apr 1, 2019
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| 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) |
|---|---|---|---|---|---|---|---|---|
| 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 | 59 | 59 | 58 | 60 | 57 | 59 | 57 | 60 |
| NOT COMPLETED | 1 | 3 | 8 | 5 | 5 | 4 | 4 | 2 |
Baseline Characteristics
| 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 |
|---|---|---|---|---|---|---|---|---|---|
| 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 Participants | 65 | 60 | 62 | 66 | 62 | 62 | 63 | 61 | 501 |
| Age (Count of Participants) | |||||||||
| <=18 years |
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%
|
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%
|
35
56.5%
|
34
51.5%
|
30
48.4%
|
38
61.3%
|
26
41.3%
|
30
49.2%
|
248
49.5%
|
| Age (years) [Mean (Standard Deviation) ] | |||||||||
| Mean (Standard Deviation) [years] |
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 (Count of Participants) | |||||||||
| Female |
23
35.4%
|
21
35%
|
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%
|
42
67.7%
|
47
71.2%
|
33
53.2%
|
39
62.9%
|
39
61.9%
|
45
73.8%
|
326
65.1%
|
| Ethnicity (NIH/OMB) (Count of 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%
|
| Race (NIH/OMB) (Count of Participants) | |||||||||
| American Indian or Alaska Native |
1
1.5%
|
0
0%
|
1
1.6%
|
1
1.5%
|
0
0%
|
2
3.2%
|
0
0%
|
1
1.6%
|
6
1.2%
|
| Asian |
0
0%
|
2
3.3%
|
2
3.2%
|
2
3%
|
1
1.6%
|
1
1.6%
|
0
0%
|
1
1.6%
|
9
1.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
1
1.6%
|
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%
|
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%
|
| Unknown or Not Reported |
1
1.5%
|
1
1.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
0.4%
|
| Region of Enrollment (Count of Participants) | |||||||||
| Canada |
8
12.3%
|
8
13.3%
|
7
11.3%
|
12
18.2%
|
10
16.1%
|
10
16.1%
|
7
11.1%
|
9
14.8%
|
71
14.2%
|
| Netherlands |
22
33.8%
|
21
35%
|
21
33.9%
|
21
31.8%
|
20
32.3%
|
20
32.3%
|
23
36.5%
|
21
34.4%
|
169
33.7%
|
| United States |
12
18.5%
|
10
16.7%
|
10
16.1%
|
12
18.2%
|
8
12.9%
|
10
16.1%
|
12
19%
|
10
16.4%
|
84
16.8%
|
| United Kingdom |
11
16.9%
|
11
18.3%
|
11
17.7%
|
11
16.7%
|
10
16.1%
|
9
14.5%
|
11
17.5%
|
12
19.7%
|
86
17.2%
|
| Germany |
12
18.5%
|
10
16.7%
|
13
21%
|
10
15.2%
|
14
22.6%
|
13
21%
|
10
15.9%
|
9
14.8%
|
91
18.2%
|
Outcome Measures
| Title | Percentage Change in LDL-C From Baseline to Day 180 |
|---|---|
| Description | Percent Change in LDL-C (beta-quantification) from Baseline to Day 180 in MITT Population |
| Time Frame | Baseline to 180 days |
Outcome Measure Data
| 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) |
|---|---|---|---|---|---|---|---|---|
| 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 |
| Measure Participants | 64 | 60 | 60 | 60 | 61 | 59 | 60 | 59 |
| Least Squares Mean (95% Confidence Interval) [Percent change] |
2.1
|
-27.9
|
-38.4
|
-41.9
|
1.8
|
-35.5
|
-44.9
|
-52.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Single Dose), 200 mg (Single Dose) |
|---|---|---|
| Comments | ||
| 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 | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Single Dose), 300 mg (Single Dose) |
|---|---|---|
| Comments | ||
| 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 | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Single Dose), 500 mg (Single Dose) |
|---|---|---|
| Comments | ||
| 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 | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Double Dose), 100 mg (Double Dose) |
|---|---|---|
| Comments | ||
| 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 | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Double Dose), 200 mg (Double Dose) |
|---|---|---|
| Comments | ||
| 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 | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Double Dose), 300 mg (Double Dose) |
|---|---|---|
| Comments | ||
| 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 | ||
| Title | Percentage Change in LDL-C From Baseline to Day 90 |
|---|---|
| Description | Percent Change in LDL-C (beta-quantification) from Baseline to Day 90 in MITT Population |
| Time Frame | Baseline to 90 days |
Outcome Measure Data
| 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 |
|---|---|---|---|---|---|
| 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) |
| Measure Participants | 60 | 59 | 125 | 120 | 118 |
| Least Squares Mean (95% Confidence Interval) [Percent change] |
-49
|
-34.2
|
-0.8
|
-41.8
|
-45.7
|
| Title | Percent Change From Baseline In LDL-C Levels At Day 60, Day 120, and Day 210 |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|---|---|---|---|---|
| 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 |
| Measure Participants | 64 | 60 | 60 | 60 | 61 | 59 | 60 | 59 |
| Day 60 |
-4.27
|
-44.32
|
-50.87
|
-49.58
|
-1.92
|
-35.73
|
-44.28
|
-50.99
|
| Day 120 |
-0.91
|
-36.94
|
-43.32
|
-46.42
|
0.17
|
-41.37
|
-49.54
|
-54.73
|
| Day 210 |
1.45
|
-28.98
|
-35.39
|
-39.2
|
0.58
|
-31.67
|
-42.59
|
-50.54
|
| Title | Number of Participants With an LDL-C Greater Than 80% of the Baseline Value at Day 180 and Day 210 |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|---|---|---|---|---|
| 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 |
| Measure Participants | 64 | 60 | 60 | 60 | 61 | 59 | 60 | 59 |
| Day 180 |
35
53.8%
|
6
10%
|
5
8.1%
|
0
0%
|
29
46.8%
|
2
3.2%
|
1
1.6%
|
0
0%
|
| Day 210 |
34
52.3%
|
8
13.3%
|
5
8.1%
|
2
3%
|
34
54.8%
|
1
1.6%
|
1
1.6%
|
1
1.6%
|
| Title | Number of Participants With Individual Responsiveness as Measured By LDL-C Levels at Day 90 and Day 180 |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|---|---|---|---|---|
| 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 |
| Measure Participants | 64 | 60 | 60 | 60 | 61 | 59 | 60 | 59 |
| Day 90 |
0
0%
|
0
0%
|
5
8.1%
|
3
4.5%
|
0
0%
|
0
0%
|
1
1.6%
|
0
0%
|
| Day 180 |
0
0%
|
0
0%
|
1
1.6%
|
2
3%
|
0
0%
|
1
1.6%
|
2
3.2%
|
3
4.9%
|
| Title | Number of Participants With Greater Or Equal To 50% LDL-C Reduction From Baseline At Day 180 |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|---|---|---|---|---|
| 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 |
| Measure Participants | 64 | 60 | 60 | 60 | 61 | 59 | 60 | 59 |
| Count of Participants [Participants] |
0
0%
|
9
15%
|
19
30.6%
|
16
24.2%
|
0
0%
|
14
22.6%
|
27
42.9%
|
32
52.5%
|
| Title | Percentage Change in PCSK9 Levels From Baseline at Day 180 |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|---|---|---|---|---|
| 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 |
| Measure Participants | 64 | 60 | 60 | 60 | 61 | 59 | 60 | 59 |
| Mean (Standard Deviation) [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)
|
| Title | Percentage Change in Other Lipids and Apolipoproteins From Baseline to Day 180 |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|---|---|---|---|---|
| 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 |
| Measure Participants | 64 | 60 | 60 | 60 | 61 | 59 | 60 | 59 |
| 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)
|
| Title | Number of Participants Who Attained Global Lipid Modification Targets for Level of Atherosclerotic Cardiovascular Disease Risk |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|---|---|---|---|---|
| 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 |
| Measure Participants | 64 | 60 | 60 | 60 | 61 | 59 | 60 | 59 |
| CVD |
45
69.2%
|
43
71.7%
|
46
74.2%
|
33
50%
|
45
72.6%
|
41
66.1%
|
39
61.9%
|
42
68.9%
|
| <70 mg/dL |
0
0%
|
16
26.7%
|
27
43.5%
|
18
27.3%
|
1
1.6%
|
24
38.7%
|
27
42.9%
|
33
54.1%
|
| Title | Percentage Change in Other Lipids and Inflammatory Markers From Baseline to Day 180 |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|---|---|---|---|---|
| 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 |
| Measure Participants | 64 | 60 | 60 | 60 | 61 | 59 | 60 | 59 |
| Triglycerides |
6.4
|
1.1
|
-12.8
|
-12.2
|
-3
|
-6.3
|
0.7
|
-14.2
|
| VLDL Cholesterol |
2.4
|
-11.6
|
-23.8
|
-14.6
|
2.7
|
-16.4
|
-21.2
|
-16
|
| Lipoprotein(a) |
0.5
|
-14.3
|
-14.3
|
-18.2
|
0
|
-14.9
|
-17.3
|
-25.6
|
| hsCRP |
-5.3
|
7.1
|
-16.2
|
-19.8
|
-20
|
-12.5
|
-16.3
|
-16.7
|
Adverse Events
| Time Frame | Treatment Emergent Adverse Events up to Day 360 | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||
| 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) | ||||||||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 1/65 (1.5%) | 0/62 (0%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/65 (4.6%) | 11/60 (18.3%) | 11/61 (18%) | 8/65 (12.3%) | 7/62 (11.3%) | 13/61 (21.3%) | 8/62 (12.9%) | 9/61 (14.8%) | ||||||||
| Blood and lymphatic system disorders | ||||||||||||||||
| Anameia | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 1/65 (1.5%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Cardiac disorders | ||||||||||||||||
| Angina pectoris | 0/65 (0%) | 1/60 (1.7%) | 1/61 (1.6%) | 1/65 (1.5%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Angina unstable | 1/65 (1.5%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Atrial flutter | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 1/65 (1.5%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 1/61 (1.6%) | ||||||||
| Acute myocardial infarction | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 1/61 (1.6%) | 0/62 (0%) | 1/61 (1.6%) | ||||||||
| Atrial fibrillation | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 1/61 (1.6%) | ||||||||
| Atrial tachycardia | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 1/61 (1.6%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Atriventricular block complete | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 1/62 (1.6%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Cardiac arrest | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 1/65 (1.5%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Coronary artery disease | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 2/61 (3.3%) | ||||||||
| Myocardial infarction | 0/65 (0%) | 1/60 (1.7%) | 0/61 (0%) | 2/65 (3.1%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 1/61 (1.6%) | ||||||||
| Pericarditis | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 1/65 (1.5%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Ventricular extrasystoles | 1/65 (1.5%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Gastrointestinal disorders | ||||||||||||||||
| Aorta-oesophageal fistula | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Constipation | 0/65 (0%) | 0/60 (0%) | 1/61 (1.6%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Gastritis | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Inguinal hernia | 0/65 (0%) | 1/60 (1.7%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| large instestine polyp | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 1/61 (1.6%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Proctitis ulcerative | 0/65 (0%) | 0/60 (0%) | 1/61 (1.6%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Rectal haemorrhage | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 1/62 (1.6%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Volvulus | 0/65 (0%) | 1/60 (1.7%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Vomiting | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 1/65 (1.5%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| General disorders | ||||||||||||||||
| Device dislocation | 0/65 (0%) | 0/60 (0%) | 1/61 (1.6%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Non-cardiac chest pain | 0/65 (0%) | 0/60 (0%) | 1/61 (1.6%) | 0/65 (0%) | 0/62 (0%) | 1/61 (1.6%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Pain | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 1/65 (1.5%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Srent-graft endoleak | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Vascular stent restenosis | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 1/61 (1.6%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Hepatobiliary disorders | ||||||||||||||||
| Hepatic haemorrhage | 0/65 (0%) | 0/60 (0%) | 1/61 (1.6%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Infections and infestations | ||||||||||||||||
| Appendicitis | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 1/61 (1.6%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Device related infection | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Erysipelas | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 1/62 (1.6%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Gastroenteritis | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 1/61 (1.6%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Implant site infection | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 1/61 (1.6%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Listeria sepsis | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Osteomyelitis | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 1/61 (1.6%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Urinary tract infection | 0/65 (0%) | 0/60 (0%) | 1/61 (1.6%) | 0/65 (0%) | 1/62 (1.6%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Urosepsis | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 1/61 (1.6%) | ||||||||
| Wound abcess | 0/65 (0%) | 0/60 (0%) | 1/61 (1.6%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||
| Concussion | 1/65 (1.5%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Facial bones fracture | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 1/61 (1.6%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Humerus fracture | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 1/61 (1.6%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Intentional overdose | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 1/62 (1.6%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Ligament sprain | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Limb crushing injury | 0/65 (0%) | 1/60 (1.7%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Multiple injuries | 0/65 (0%) | 0/60 (0%) | 1/61 (1.6%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Pneumothorax traumatic | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 1/65 (1.5%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Post procedural complication | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 1/65 (1.5%) | 0/62 (0%) | 0/61 (0%) | 2/62 (3.2%) | 0/61 (0%) | ||||||||
| Post procedural haemorrhage | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 1/65 (1.5%) | 1/62 (1.6%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Thoracic vertebral fracture | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 1/65 (1.5%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Traumatic haemothorax | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 1/65 (1.5%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Upperlimb fracture | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 1/65 (1.5%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Weaning failure | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Investigations | ||||||||||||||||
| Haemoglobin decreased | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 1/62 (1.6%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Platelet count decreased | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 1/62 (1.6%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Transaminases increased | 0/65 (0%) | 0/60 (0%) | 1/61 (1.6%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Metabolism and nutrition disorders | ||||||||||||||||
| Dehydration | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Hypoglycemia | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 1/61 (1.6%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Muscle necrosis | 1/65 (1.5%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Osteitis | 0/65 (0%) | 1/60 (1.7%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Osteoarthritis | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 1/61 (1.6%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| Adeoncarcinoma of colon | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Bladder cancer | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Bladder transitional cell carcinoma stage 0 | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 1/61 (1.6%) | ||||||||
| Gastrointestinal tract adenoma | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Glioblastoma | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 1/61 (1.6%) | ||||||||
| Hepatocellular carcinoma | 0/65 (0%) | 0/60 (0%) | 1/61 (1.6%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Intestinal adenocarcinoma | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 1/61 (1.6%) | ||||||||
| Non-small cell lung cancer stage 1 | 0/65 (0%) | 0/60 (0%) | 1/61 (1.6%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Oesophageal adenocarcinoma | 0/65 (0%) | 1/60 (1.7%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Pituitary tumour benign | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 1/65 (1.5%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Prostate cancer | 0/65 (0%) | 2/60 (3.3%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Squamous cell carcinoma of lung | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 1/65 (1.5%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Squamous cell carcinoma of skin | 0/65 (0%) | 1/60 (1.7%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Tongue neoplasm malignant | 0/65 (0%) | 1/60 (1.7%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Nervous system disorders | ||||||||||||||||
| Carpal tunnel syndrome | 0/65 (0%) | 1/60 (1.7%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Ischaemic stroke | 0/65 (0%) | 0/60 (0%) | 1/61 (1.6%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Lacunar stroke | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 1/61 (1.6%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Neuropathy peripheral | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 1/61 (1.6%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Spinal cord ischaemia | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Syncope | 0/65 (0%) | 1/60 (1.7%) | 1/61 (1.6%) | 0/65 (0%) | 1/62 (1.6%) | 0/61 (0%) | 1/62 (1.6%) | 1/61 (1.6%) | ||||||||
| Renal and urinary disorders | ||||||||||||||||
| Acute kidney injury | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Calculus urinary | 0/65 (0%) | 1/60 (1.7%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Stress urinary incontinence | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 1/62 (1.6%) | 0/61 (0%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Chronic obstructive pulmonary disease | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Vascular disorders | ||||||||||||||||
| Aortic dissection | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Hypotension | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 1/61 (1.6%) | 0/62 (0%) | 0/61 (0%) | ||||||||
| Intermittent claudication | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Orthostatic hypotension | 0/65 (0%) | 0/60 (0%) | 0/61 (0%) | 0/65 (0%) | 0/62 (0%) | 0/61 (0%) | 0/62 (0%) | 1/61 (1.6%) | ||||||||
Other (Not Including 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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 50/65 (76.9%) | 49/60 (81.7%) | 49/61 (80.3%) | 54/65 (83.1%) | 51/62 (82.3%) | 47/61 (77%) | 49/62 (79%) | 51/61 (83.6%) | ||||||||
| Cardiac disorders | ||||||||||||||||
| Angina pectoris | 1/65 (1.5%) | 2/60 (3.3%) | 4/61 (6.6%) | 1/65 (1.5%) | 2/62 (3.2%) | 0/61 (0%) | 2/62 (3.2%) | 0/61 (0%) | ||||||||
| Gastrointestinal disorders | ||||||||||||||||
| Abdominal pain | 2/65 (3.1%) | 3/60 (5%) | 2/61 (3.3%) | 0/65 (0%) | 3/62 (4.8%) | 2/61 (3.3%) | 1/62 (1.6%) | 4/61 (6.6%) | ||||||||
| Constipation | 1/65 (1.5%) | 4/60 (6.7%) | 2/61 (3.3%) | 1/65 (1.5%) | 2/62 (3.2%) | 0/61 (0%) | 2/62 (3.2%) | 1/61 (1.6%) | ||||||||
| Diarrhoea | 1/65 (1.5%) | 1/60 (1.7%) | 4/61 (6.6%) | 4/65 (6.2%) | 2/62 (3.2%) | 3/61 (4.9%) | 7/62 (11.3%) | 5/61 (8.2%) | ||||||||
| Nausea | 2/65 (3.1%) | 1/60 (1.7%) | 1/61 (1.6%) | 4/65 (6.2%) | 3/62 (4.8%) | 2/61 (3.3%) | 4/62 (6.5%) | 3/61 (4.9%) | ||||||||
| Vomiting | 0/65 (0%) | 1/60 (1.7%) | 2/61 (3.3%) | 1/65 (1.5%) | 0/62 (0%) | 0/61 (0%) | 4/62 (6.5%) | 0/61 (0%) | ||||||||
| General disorders | ||||||||||||||||
| Fatigue | 5/65 (7.7%) | 2/60 (3.3%) | 4/61 (6.6%) | 2/65 (3.1%) | 6/62 (9.7%) | 2/61 (3.3%) | 0/62 (0%) | 1/61 (1.6%) | ||||||||
| Infections and infestations | ||||||||||||||||
| Gastroenteritis | 0/65 (0%) | 3/60 (5%) | 2/61 (3.3%) | 1/65 (1.5%) | 2/62 (3.2%) | 3/61 (4.9%) | 1/62 (1.6%) | 1/61 (1.6%) | ||||||||
| Influenza | 3/65 (4.6%) | 3/60 (5%) | 4/61 (6.6%) | 5/65 (7.7%) | 2/62 (3.2%) | 3/61 (4.9%) | 4/62 (6.5%) | 5/61 (8.2%) | ||||||||
| Nasopharyngitis | 4/65 (6.2%) | 8/60 (13.3%) | 9/61 (14.8%) | 9/65 (13.8%) | 8/62 (12.9%) | 8/61 (13.1%) | 5/62 (8.1%) | 11/61 (18%) | ||||||||
| Upper respiratory tract infection | 2/65 (3.1%) | 2/60 (3.3%) | 4/61 (6.6%) | 5/65 (7.7%) | 2/62 (3.2%) | 2/61 (3.3%) | 1/62 (1.6%) | 3/61 (4.9%) | ||||||||
| Urinary tract infection | 1/65 (1.5%) | 1/60 (1.7%) | 5/61 (8.2%) | 0/65 (0%) | 4/62 (6.5%) | 1/61 (1.6%) | 1/62 (1.6%) | 2/61 (3.3%) | ||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||
| Contusion | 1/65 (1.5%) | 1/60 (1.7%) | 2/61 (3.3%) | 2/65 (3.1%) | 5/62 (8.1%) | 3/61 (4.9%) | 1/62 (1.6%) | 2/61 (3.3%) | ||||||||
| Fall | 1/65 (1.5%) | 0/60 (0%) | 1/61 (1.6%) | 1/65 (1.5%) | 1/62 (1.6%) | 4/61 (6.6%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Investigations | ||||||||||||||||
| Blood creatine phosphokinase increased | 3/65 (4.6%) | 1/60 (1.7%) | 1/61 (1.6%) | 0/65 (0%) | 5/62 (8.1%) | 0/61 (0%) | 3/62 (4.8%) | 0/61 (0%) | ||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Arthralgia | 2/65 (3.1%) | 4/60 (6.7%) | 4/61 (6.6%) | 4/65 (6.2%) | 1/62 (1.6%) | 2/61 (3.3%) | 5/62 (8.1%) | 3/61 (4.9%) | ||||||||
| Back pain | 5/65 (7.7%) | 4/60 (6.7%) | 4/61 (6.6%) | 4/65 (6.2%) | 2/62 (3.2%) | 6/61 (9.8%) | 1/62 (1.6%) | 4/61 (6.6%) | ||||||||
| Musculoskeletal pain | 1/65 (1.5%) | 2/60 (3.3%) | 0/61 (0%) | 1/65 (1.5%) | 4/62 (6.5%) | 0/61 (0%) | 0/62 (0%) | 6/61 (9.8%) | ||||||||
| Myalgia | 3/65 (4.6%) | 2/60 (3.3%) | 6/61 (9.8%) | 3/65 (4.6%) | 3/62 (4.8%) | 7/61 (11.5%) | 5/62 (8.1%) | 5/61 (8.2%) | ||||||||
| Pain in extremity | 2/65 (3.1%) | 2/60 (3.3%) | 1/61 (1.6%) | 2/65 (3.1%) | 4/62 (6.5%) | 1/61 (1.6%) | 4/62 (6.5%) | 1/61 (1.6%) | ||||||||
| Nervous system disorders | ||||||||||||||||
| Dizziness | 3/65 (4.6%) | 1/60 (1.7%) | 2/61 (3.3%) | 2/65 (3.1%) | 6/62 (9.7%) | 3/61 (4.9%) | 3/62 (4.8%) | 3/61 (4.9%) | ||||||||
| Headache | 6/65 (9.2%) | 2/60 (3.3%) | 2/61 (3.3%) | 2/65 (3.1%) | 5/62 (8.1%) | 5/61 (8.2%) | 1/62 (1.6%) | 5/61 (8.2%) | ||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Cough | 2/65 (3.1%) | 4/60 (6.7%) | 7/61 (11.5%) | 3/65 (4.6%) | 3/62 (4.8%) | 1/61 (1.6%) | 6/62 (9.7%) | 3/61 (4.9%) | ||||||||
| Epistaxis | 4/65 (6.2%) | 0/60 (0%) | 0/61 (0%) | 1/65 (1.5%) | 1/62 (1.6%) | 0/61 (0%) | 1/62 (1.6%) | 0/61 (0%) | ||||||||
| Vascular disorders | ||||||||||||||||
| Hypertension | 0/65 (0%) | 2/60 (3.3%) | 3/61 (4.9%) | 1/65 (1.5%) | 3/62 (4.8%) | 4/61 (6.6%) | 2/62 (3.2%) | 1/61 (1.6%) | ||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
| Name/Title | Global Health Science Center |
|---|---|
| Organization | The Medicine's Company |
| Phone | 1-888-997-6326 |
| Medical.Information@themedco.com |
Responsible Party:
The Medicines Company
ClinicalTrials.gov Identifier:
NCT02597127
Other Study ID Numbers:
- MDCO-PCS-15-01
First Posted:
Nov 5, 2015
Last Update Posted:
May 17, 2019
Last Verified:
Apr 1, 2019