Homozygous Familial Hypercholesterolemia
Conditions
Keywords
HoFH
Brief summary
This study was a Phase III,A two-part (double-blind placebo-controlled/open-label) multicenter study to evaluate safety, tolerability, and efficacy of inclisiran in subjects with homozygous familial hypercholesterolemia (HoFH).
Detailed description
This study had two sequential parts: * Part 1: 6-month double-blind period in which subjects were randomized to receive either inclisiran or placebo * Part 2: 18-month open-label follow-up period; placebo-treated subjects from Part 1 were transitioned to inclisiran at Day 180 and all subjects who participated in an open-label follow-up period of inclisiran only
Interventions
DRUGInclisiran Sodium for injection
Inclisiran is a synthetic, chemically modified small interfering ribonucleic acid (siRNA) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) messenger ribonucleic acid (mRNA) with a covalently attached triantennary N-acetylgalactosamine (GalNAc) ligand.
DRUGPlacebo
Sterile normal saline (0.9% sodium chloride in water for injection)
DRUGPlacebos
Sterile normal saline (0.9% sodium chloride in water for injection)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
1. Diagnosis of HoFH by genetic confirmation or a clinical diagnosis based on a history of an untreated LDL-C concentration \>500 mg/dL (13 mmol/L) together with either xanthoma before 10 years of age or evidence of heterozygous familial hypercholesterolemia in both parents 2. Stable on a low-fat diet. 3. Subjects on statins should be receiving a maximally tolerated dose. Maximum tolerated dose is defined as the maximum dose of statin that can be taken on a regular basis without intolerable adverse events. 4. Subjects not receiving statins must have documented evidence of intolerance to at least two different statins. 5. Subjects 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. 6. Fasting central laboratory LDL-C concentration ≥130 mg/dL (3.4 mmol/L). 7. Triglyceride concentration \<400 mg/dL (4.5 mmol/L) 8. No current or planned renal dialysis or renal transplantation 9. Subjects on a documented regimen of LDL or plasma apheresis will be allowed to continue the apheresis during the study, if needed. 10. Subjects must be willing and able to give written informed consent before initiation of any study-related procedures. The subject should be willing to comply with all required study procedures. 11. Willing to follow all study procedures including adherence to dietary guidelines, study visits, fasting blood draws, and compliance with study treatment regimens.
Exclusion criteria
1. Use of Mipomersen or Lomitapide therapy within 5 months of screening 2. Treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9 3. New York Heart Association (NYHA) class IV heart failure or last known left ventricular ejection fraction \<25% 4. Major adverse cardiovascular event within 3 months prior to randomization 5. Planned cardiac surgery or revascularization 6. Uncontrolled severe hypertension: systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg prior to randomization despite anti-hypertensive therapy 7. Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST), elevation \>3x ULN, or total bilirubin \>2x upper limit of normal (ULN) at screening confirmed by a repeat measurement at least 1 week apart 8. Severe concomitant noncardiovascular disease that carries the risk of reducing life expectancy to less than the duration of the trial 9. History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or commencement of systemic therapy as treatment during the 3 years prior to randomization 10. Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least one acceptable effective method of contraception (eg, oral contraceptives, barrier methods, approved contraceptive implant, long- term injectable contraception, intrauterine device) for the entire duration of the study. Exemptions from this criterion: 1. Women \>2 years postmenopausal (defined as 1 year or longer since their last menstrual period) AND more than 55 years of age 2. Postmenopausal women (as defined above) and less than 55 years of age with a negative pregnancy test within 24 hours of enrolment 3. Women who are surgically sterilized at least 3 months prior to enrolment 11. Known history of alcohol and/or drug abuse within 5 years 12. Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to: 1. Subjects who are unable to communicate or to cooperate with the investigator. 2. Unable to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study (including subjects whose cooperation is doubtful due to drug abuse or alcohol dependency) 3. Unlikely to comply with the protocol requirements, instructions, and study-related restrictions (eg, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study) 4. Have any medical or surgical condition, which in the opinion of the investigator would put the subject at increased risk from participating in the study 5. Persons directly involved in the conduct of the study 13. 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 subject at significant risk (according to investigator's \[or delegate\] judgment) if he/she participates in the clinical study 14. Any underlying known disease, or surgical, physical, or medical condition that, in the opinion of the Investigator, might interfere with the interpretation of clinical study results 15. Treatment with other investigational medicinal products or devices within 30 days or 5 half-lives of the screening visit, whichever is longer 16. Previous participation in the study 17. Hypersensitivity to any of the ingredients of Inclisiran The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 150 | Baseline, Day 150 | Percentage Change in LDL-C levels from Baseline to Day 150 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150, 180 | Percentage Change in PCSK9 from baseline to subsequent visits up to Day 180 |
| Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 270, 330, 450, 510, 630, 690, and 720 | Percentage Change in PCSK9 from baseline to subsequent visits up to Day 720 |
| Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 150 | Baseline, Day 150 | Absolute Change in LDL-C levels (mg/dL) from baseline to Day 150 |
| Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150, 180 | Percentage Change in LDL-C levels from baseline to subsequent visits on Days 90, 150, and 180 |
| Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 270, 330, 450, 510, 630, 690, and 720 | Percentage Change in LDL-C levels from baseline to subsequent visits up to Day 720 |
| Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150, 180 | Absolute change in LDL-C levels (mg/dL) from baseline to subsequent visits on Days 90, 150 and 180 based on the |
| Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150, 180 | Absolute Change in PCSK9 from baseline to subsequent visits up to Day 180 |
| Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 270, 330, 450, 510, 630, 690, and 720 | Absolute Change in PCSK9 from baseline to subsequent visits up to Day 720 |
| Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150 and 180 | Percentage change in total cholesterol from baseline to subsequent visits up to Day 180 |
| Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150, 180 | Absolute Change in total cholesterol from baseline to subsequent visits up to Day 180 |
| Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 270, 330, 450, 510, 630, 690, and 720 | Percentage change in total cholesterol from baseline to subsequent visits up to Day 720 |
| Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 270, 330, 450, 510, 630, 690, and 720 | Absolute Change in total cholesterol from baseline to subsequent visits up to Day 720 |
| Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150, 180 | Percentage change in Apolipoprotein B (apoB) from baseline to subsequent visits up to Day 180 demonstrated by Mixed Model Repeated Measures statisitical method. |
| Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 270, 330, 450, 510, 630, 690, and 720 | Percentage Change in Apolipoprotein B (apoB) from baseline to subsequent visits up to Day 720 |
| Absolute Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150, 180 | Absolute change in Apolipoprotein B (apoB) from baseline to subsequent visits up to Day 180 |
| Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 270, 330, 450, 510, 630, 690, and 720 | Absolute Change in Apolipoprotein B (Apo B) from baseline to subsequent visits up to Day 720 |
| Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150, 180 | Percentage change in non-HDL-C levels from baseline to subsequent visits up to Day 180 |
| Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 270, 330, 450, 510, 630, 690, and 720 | Percentage Change in non-HDL-C from Baseline to subsequent visits up to Day 720 |
| Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150, 180 | Absolute change in non-HDL-C levels from Baseline to subsequent visits up to Day 180 |
| Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 270, 330, 450, 510, 630, 690, and 720 | Absolute Change in non-HDL Cholesterol (non-HDL-C) from Baseline to Subsequent Visits up to Day 720 |
| Individual Responsiveness of Subjects: Part 1 | Days 150, 180 | Individual Responsiveness of Subjects defined as the number of subjects reaching on treatment LDL-C levels of \<25 mg/dL, \<50 mg/dL, \<70 mg/dL, and \<100 mg/dL up to Day 180 |
| Individual Responsiveness of Subjects: Part 2 | Days 330, 510, 690 and 720 | Individual Responsiveness of Subjects defined as the number of subjects reaching on treatment LDL-C levels of \<25 mg/dL, \<50 mg/dL, \<70 mg/dL, and \<100 mg/dL up to Day 720 |
| Proportional Responsiveness: Part 1 | Days 150, 180 | Number of participants in each group who attain global lipid targets for their indication |
| Proportional Responsiveness of Subjects: Part 2 | Days 330, 510, 690 and 720 | Number of participants in each group who attain global lipid targets for their indication |
| LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 | Baseline, Days 90, 150, 180 | Proportion of subjects in each group with ≥20% or ≥30% LDL-C reduction from Baseline in Part 1 (Days 90, 150, 180) |
| LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 | Baseline, Days 330, 510, 690, and 720 | Proportion of subjects in each group with ≥20% or ≥30% LDL-C reduction from Baseline in Part 2 (Days 330, 510, 690, and 720) |
| Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150, 180 | Percentage Change in HDL-C levels (mg/dL) from baseline to subsequent visits on Day 90, 150, and 180 |
| Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 330, 450, 510, 630, 690, and 720 | Percentage change in LDL-C levels from Baseline to Subsequent Visits up to Day 720 |
| Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150, 180 | Absolute Change in HDL-C levels (mg/dL) from baseline to subsequent visits on Day 90, 150, and 180 |
| Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 330, 450, 510, 630, 690, and 720 | Absolute change in LDL-C levels from Baseline to Subsequent Visits up to Day 720 |
| Absolute Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150, 180 | Absolute Change in VLDL-C levels from baseline to subsequent visits on Days 90, 150, and 180 |
| Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 330, 450, 510, 630, 690, and 720 | Absolute change in VLDL-C levels from Baseline to Subsequent Visits up to Day 720 |
| Percent Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150, 180 | Percentage Change in VLDL-C levels (mg/dL) from baseline to subsequent visits on Days 90, 150, and 180 |
| Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 330, 450, 510, 630, 690, and 720 | Percentage change in VLDL-C levels from Baseline to Subsequent Visits up to Day 720 |
| Absolute Change in Apolipoprotein A-1 (Apo-A1) mg/dL From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150, 180 | Absolute Change in Apolipoprotein A-1 (Apo-A1) from baseline to subsequent visits on Days 90, 150, and 180 |
| Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 330, 450, 510, 630, 690, and 720 | Absolute change in Apolipoprotein A-1 (Apo-A1) from Baseline to Subsequent Visits up to Day 720 |
| Percent Change in Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150, 180 | Percentage Change in Apolipoprotein A-1 (Apo-A1) from baseline to subsequent visits on Day 90, 150, and 180 |
| Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 330, 450, 510, 630, 690, and 720 | Percentage change in Apolipoprotein A-1 (Apo-A1) from Baseline to Subsequent Visits up to Day 720 |
| Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150, 180 | Percentage Change in Lp(a) from Baseline to Subsequent Visits up to Day 180 |
| Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 330, 450, 510, 630, 690, and 720 | Percentage change in Lp(a) from Baseline to Subsequent Visits up to Day 720 |
| Percent Change in Total Cholesterol From Baseline to Day 150 | Baseline, Day 150 | Percentage change in total cholesterol from baseline to Day 150 as demonstrated using the ANCOVA statisitical model. |
| Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 | Baseline, Days 90, 150, 180 | Absolute Change in Lp(a) from baseline to subsequent visits up to Day 180 |
| Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 330, 450, 510, 630, 690, and 720 | Absolute change in Lp(a) from Baseline to Subsequent Visits up to Day 720 |
| Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 | Baseline, Days 90, 150, 180 | Percent change in hsCRP from Baseline to subsequent visits up to Day 180 |
| Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Baseline, Days 270, 330, 450, 510, 630, 690, and 720 | Absolute change in LDL-C levels from Baseline to Subsequent Visits up to Day 720 |
| Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 | Baseline, Days 90, 150, 180 | Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) from Baseline to subsequent visits up to Day 180 |
| Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Baseline, Days 330, 510, 690, 720 | Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) from baseline to subsequent visits up to Day 720 |
| Percent Change in Apo-B From Baseline to Day 150 | Baseline, Day 150 | Percentage change in Apo-B from baseline to Day 150 as demonstrated using the ANCOVA statisitical model. |
| Percent Change in Non-HDL-C From Baseline to Day 150 | Baseline, Day 150 | Percentage Change in non-HDL-C from baseline to Day 150 as demonstrated using the ANCOVA statisitical model. |
| Proportion of Subjects With ≥30% LDL-C Reduction of From Baseline at Day 150 | Baseline, Day 150 | Number of participants in each group with ≥30% LDL-C reduction from baseline at Day 150 using the Regression Logistic Statistical Model |
| Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Baseline, Days 330, 510 ,690, 720 | Percentage change in hsCRP from baseline to subsequent visits up to Day 720 |
Countries
Hong Kong, Israel, Russia, Serbia, South Africa, Taiwan, Turkey (Türkiye), Ukraine
Participant flow
Recruitment details
Overall, 56 subjects were enrolled and 53 subjects completed through Day 180 (Part 1) and went into the Open-Label period (Part 2), in which 47 subjects completed.
Participants by arm
| Arm | Count |
|---|---|
| Inclisiran Participants who received a dose of inclisiran sodium for injection administered by sub-cutaneous (SC) injection | 37 |
| Placebo Participants who received a dose of placebo administered by sub-cutaneous (SC) injection | 19 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part 1: Double-Blind Period | Other reason | 1 | 0 | 0 | 0 |
| Part 1: Double-Blind Period | Withdrawal by Subject | 2 | 0 | 0 | 0 |
| Part 2: Open-Label Period | Death | 0 | 0 | 3 | 0 |
| Part 2: Open-Label Period | Other reason | 0 | 0 | 0 | 1 |
| Part 2: Open-Label Period | Withdrawal by Subject | 0 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Inclisiran | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 0 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants | 19 Participants | 53 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 31 Participants | 17 Participants | 48 Participants |
| Sex: Female, Male Female | 23 Participants | 11 Participants | 34 Participants |
| Sex: Female, Male Male | 14 Participants | 8 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 37 | 0 / 19 | 0 / 56 | 3 / 53 |
| other Total, other adverse events | 12 / 37 | 6 / 19 | 18 / 56 | 29 / 53 |
| serious Total, serious adverse events | 2 / 37 | 1 / 19 | 3 / 56 | 11 / 53 |
Outcome results
Primary
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 150
Percentage Change in LDL-C levels from Baseline to Day 150
Time frame: Baseline, Day 150
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1 - Placebo | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 150 | 2.39 Percentage change |
| Part 1 - Inclisiran | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 150 | 0.70 Percentage change |
p-value: 0.904795% CI: [-29.19, 25.83]ANCOVA
Secondary
Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720
Absolute change in Apolipoprotein A-1 (Apo-A1) from Baseline to Subsequent Visits up to Day 720
Time frame: Baseline, Days 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 330 | 0.9 mg/dL | Standard Deviation 14.14 |
| Part 1 - Placebo | Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 450 | 4.9 mg/dL | Standard Deviation 14.04 |
| Part 1 - Placebo | Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 510 | 6.7 mg/dL | Standard Deviation 20.39 |
| Part 1 - Placebo | Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 630 | 5.4 mg/dL | Standard Deviation 15.59 |
| Part 1 - Placebo | Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 690 | 6.9 mg/dL | Standard Deviation 17.07 |
| Part 1 - Placebo | Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 720 | 3.9 mg/dL | Standard Deviation 15.15 |
| Part 1 - Inclisiran | Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 690 | 9.3 mg/dL | Standard Deviation 15.69 |
| Part 1 - Inclisiran | Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 330 | 1.2 mg/dL | Standard Deviation 13.85 |
| Part 1 - Inclisiran | Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 630 | 1.3 mg/dL | Standard Deviation 13.11 |
| Part 1 - Inclisiran | Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 450 | 4.7 mg/dL | Standard Deviation 16.59 |
| Part 1 - Inclisiran | Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 720 | 6.9 mg/dL | Standard Deviation 11.3 |
| Part 1 - Inclisiran | Absolute Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 510 | 7.8 mg/dL | Standard Deviation 16.32 |
Secondary
Absolute Change in Apolipoprotein A-1 (Apo-A1) mg/dL From Baseline to Subsequent Visits up to Day 180
Absolute Change in Apolipoprotein A-1 (Apo-A1) from baseline to subsequent visits on Days 90, 150, and 180
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Absolute Change in Apolipoprotein A-1 (Apo-A1) mg/dL From Baseline to Subsequent Visits up to Day 180 | Day 90 | 2.6 mg/dL |
| Part 1 - Placebo | Absolute Change in Apolipoprotein A-1 (Apo-A1) mg/dL From Baseline to Subsequent Visits up to Day 180 | Day 150 | 4.0 mg/dL |
| Part 1 - Placebo | Absolute Change in Apolipoprotein A-1 (Apo-A1) mg/dL From Baseline to Subsequent Visits up to Day 180 | Day 180 | 1.4 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Apolipoprotein A-1 (Apo-A1) mg/dL From Baseline to Subsequent Visits up to Day 180 | Day 90 | 0.6 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Apolipoprotein A-1 (Apo-A1) mg/dL From Baseline to Subsequent Visits up to Day 180 | Day 150 | -1.4 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Apolipoprotein A-1 (Apo-A1) mg/dL From Baseline to Subsequent Visits up to Day 180 | Day 180 | -1.3 mg/dL |
Comparison: Day 90p-value: 0.684895% CI: [-11.5, 7.6]Mixed Model Repeated Measures
Comparison: Day 150p-value: 0.407595% CI: [-18.5, 7.6]Mixed Model Repeated Measures
Comparison: Day 180p-value: 0.599895% CI: [-13.4, 7.8]Mixed Model Repeated Measures
Secondary
Absolute Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180
Absolute change in Apolipoprotein B (apoB) from baseline to subsequent visits up to Day 180
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Absolute Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 | Day 90 | 10.0 mg/dL |
| Part 1 - Placebo | Absolute Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 | Day 150 | 3.3 mg/dL |
| Part 1 - Placebo | Absolute Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 | Day 180 | 8.4 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 | Day 90 | -9.4 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 | Day 150 | -1.4 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 | Day 180 | -7.4 mg/dL |
Comparison: Day 90p-value: 0.204495% CI: [-49.7, 10.9]Mixed Model Repeated Measures
Comparison: Day 150p-value: 0.787595% CI: [-39.9, 30.4]Mixed Model Repeated Measures
Comparison: Day 180p-value: 0.319395% CI: [-47.3, 15.7]Mixed Model Repeated Measures
Secondary
Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720
Absolute Change in Apolipoprotein B (Apo B) from baseline to subsequent visits up to Day 720
Time frame: Baseline, Days 270, 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 | Day 450 | 3.0 mg/dL | Standard Deviation 53.54 |
| Part 1 - Placebo | Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 | Day 510 | -3.5 mg/dL | Standard Deviation 58.45 |
| Part 1 - Placebo | Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -15.4 mg/dL | Standard Deviation 38.17 |
| Part 1 - Placebo | Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -10.6 mg/dL | Standard Deviation 61.77 |
| Part 1 - Placebo | Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -22.1 mg/dL | Standard Deviation 45.29 |
| Part 1 - Placebo | Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 | Day 270 | -1.3 mg/dL | Standard Deviation 83.72 |
| Part 1 - Placebo | Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 | Day 330 | -11.5 mg/dL | Standard Deviation 66.78 |
| Part 1 - Inclisiran | Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 | Day 450 | -6.9 mg/dL | Standard Deviation 61.89 |
| Part 1 - Inclisiran | Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -13.0 mg/dL | Standard Deviation 55.14 |
| Part 1 - Inclisiran | Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 | Day 510 | 1.1 mg/dL | Standard Deviation 70.4 |
| Part 1 - Inclisiran | Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 | Day 330 | -7.3 mg/dL | Standard Deviation 56.52 |
| Part 1 - Inclisiran | Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -10.1 mg/dL | Standard Deviation 57.06 |
| Part 1 - Inclisiran | Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 | Day 270 | -1.9 mg/dL | Standard Deviation 51.79 |
| Part 1 - Inclisiran | Absolute Change in Apolipoprotein B (Apo B) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -10.3 mg/dL | Standard Deviation 54.82 |
Secondary
Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180
Absolute Change in HDL-C levels (mg/dL) from baseline to subsequent visits on Day 90, 150, and 180
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 90 | -0.0 mg/dL |
| Part 1 - Placebo | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 150 | 1.0 mg/dL |
| Part 1 - Placebo | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 180 | -1.2 mg/dL |
| Part 1 - Inclisiran | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 180 | 0.0 mg/dL |
| Part 1 - Inclisiran | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 90 | 0.2 mg/dL |
| Part 1 - Inclisiran | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 150 | -0.0 mg/dL |
Comparison: Day 90p-value: 0.923795% CI: [-4, 4.4]Mixed Model Repeated Measures
Comparison: Day 150p-value: 0.717795% CI: [-6.5, 4.5]Mixed Model Repeated Measures
Comparison: Day 180p-value: 0.541695% CI: [-2.9, 5.4]Mixed Model Repeated Measures
Secondary
Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720
Absolute change in LDL-C levels from Baseline to Subsequent Visits up to Day 720
Time frame: Baseline, Days 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 330 | 1.6 mg/dL | Standard Deviation 6.05 |
| Part 1 - Placebo | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 450 | 0.9 mg/dL | Standard Deviation 6.04 |
| Part 1 - Placebo | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 510 | 1.5 mg/dL | Standard Deviation 8.78 |
| Part 1 - Placebo | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -0.7 mg/dL | Standard Deviation 7.35 |
| Part 1 - Placebo | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -0.6 mg/dL | Standard Deviation 9.57 |
| Part 1 - Placebo | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -1.5 mg/dL | Standard Deviation 7.22 |
| Part 1 - Inclisiran | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 690 | 1.0 mg/dL | Standard Deviation 8.31 |
| Part 1 - Inclisiran | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 330 | 0.9 mg/dL | Standard Deviation 6.85 |
| Part 1 - Inclisiran | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -0.2 mg/dL | Standard Deviation 7.7 |
| Part 1 - Inclisiran | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 450 | 1.4 mg/dL | Standard Deviation 8.53 |
| Part 1 - Inclisiran | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 720 | 0.8 mg/dL | Standard Deviation 7.34 |
| Part 1 - Inclisiran | Absolute Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 510 | 2.5 mg/dL | Standard Deviation 7.86 |
Secondary
Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1
Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) from Baseline to subsequent visits up to Day 180
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population (Part 1): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 | Day 90 | -3.2 mg/L | Standard Deviation 9.46 |
| Part 1 - Placebo | Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 | Day 150 | 0.5 mg/L | Standard Deviation 15.07 |
| Part 1 - Placebo | Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 | Day 180 | -3.8 mg/L | Standard Deviation 9.33 |
| Part 1 - Inclisiran | Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 | Day 90 | 0.7 mg/L | Standard Deviation 4.25 |
| Part 1 - Inclisiran | Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 | Day 150 | 1.1 mg/L | Standard Deviation 6.51 |
| Part 1 - Inclisiran | Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 | Day 180 | 0.2 mg/L | Standard Deviation 3.75 |
Secondary
Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2
Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) from baseline to subsequent visits up to Day 720
Time frame: Baseline, Days 330, 510, 690, 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Day 330 | -4.0 mg/L | Standard Deviation 9.98 |
| Part 1 - Placebo | Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Day 510 | -3.4 mg/L | Standard Deviation 10.07 |
| Part 1 - Placebo | Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Day 690 | -4.7 mg/L | Standard Deviation 10.21 |
| Part 1 - Placebo | Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Day 720 | -3.7 mg/L | Standard Deviation 9.86 |
| Part 1 - Inclisiran | Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Day 720 | -0.2 mg/L | Standard Deviation 4.25 |
| Part 1 - Inclisiran | Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Day 330 | -0.4 mg/L | Standard Deviation 2.81 |
| Part 1 - Inclisiran | Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Day 690 | 0.7 mg/L | Standard Deviation 3.94 |
| Part 1 - Inclisiran | Absolute Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Day 510 | 0.9 mg/L | Standard Deviation 4.75 |
Secondary
Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180
Absolute Change in Lp(a) from baseline to subsequent visits up to Day 180
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 | Day 90 | 5.8 nmol/L |
| Part 1 - Placebo | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 | Day 150 | 3.9 nmol/L |
| Part 1 - Placebo | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 | Day 180 | 1.2 nmol/L |
| Part 1 - Inclisiran | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 | Day 90 | -3.8 nmol/L |
| Part 1 - Inclisiran | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 | Day 150 | -5.6 nmol/L |
| Part 1 - Inclisiran | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 | Day 180 | -5.1 nmol/L |
Comparison: Day 90p-value: 0.307795% CI: [-28.3, 9.1]Mixed Model Repeated Measures
Comparison: Day 150p-value: 0.362895% CI: [-30.1, 11.2]Mixed Model Repeated Measures
Comparison: Day 180p-value: 0.466995% CI: [-23.2, 10.8]Mixed Model Repeated Measures
Secondary
Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720
Absolute change in Lp(a) from Baseline to Subsequent Visits up to Day 720
Time frame: Baseline, Days 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 330 | -3.1 nmol/L | Standard Deviation 36.71 |
| Part 1 - Placebo | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 510 | 14.5 nmol/L | Standard Deviation 50.25 |
| Part 1 - Placebo | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 720 | -6.0 nmol/L | Standard Deviation 48.12 |
| Part 1 - Placebo | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 630 | -2.4 nmol/L | Standard Deviation 31.18 |
| Part 1 - Placebo | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 450 | -3.8 nmol/L | Standard Deviation 47.48 |
| Part 1 - Placebo | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 690 | -5.3 nmol/L | Standard Deviation 26.52 |
| Part 1 - Inclisiran | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 450 | 3.1 nmol/L | Standard Deviation 41.28 |
| Part 1 - Inclisiran | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 720 | 5.2 nmol/L | Standard Deviation 30.44 |
| Part 1 - Inclisiran | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 330 | -5.2 nmol/L | Standard Deviation 30.65 |
| Part 1 - Inclisiran | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 690 | 5.8 nmol/L | Standard Deviation 26.46 |
| Part 1 - Inclisiran | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 510 | 18.4 nmol/L | Standard Deviation 53.31 |
| Part 1 - Inclisiran | Absolute Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 630 | 13.7 nmol/L | Standard Deviation 50.77 |
Secondary
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 150
Absolute Change in LDL-C levels (mg/dL) from baseline to Day 150
Time frame: Baseline, Day 150
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1 - Placebo | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 150 | -8.82 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 150 | -2.35 mg/dL |
p-value: 0.868595% CI: [-70.11, 83.05]ANCOVA
Secondary
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180
Absolute change in LDL-C levels (mg/dL) from baseline to subsequent visits on Days 90, 150 and 180 based on the
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 90 | 3.6 mg/dL |
| Part 1 - Placebo | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 150 | -17.2 mg/dL |
| Part 1 - Placebo | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 180 | -7.0 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 90 | -16.3 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 150 | 0.5 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 180 | -14.5 mg/dL |
Comparison: Day 90p-value: 0.458995% CI: [-73.3, 33.6]Mixed Model Repeated Measures
Comparison: Day 150p-value: 0.595695% CI: [-48.8, 84.3]Mixed Model Repeated Measures
Comparison: Day 180p-value: 0.786195% CI: [-62.7, 47.7]Mixed Model Repeated Measures
Secondary
Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720
Absolute change in LDL-C levels from Baseline to Subsequent Visits up to Day 720
Time frame: Baseline, Days 270, 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 450 | -12.3 mg/dL | Standard Deviation 108.49 |
| Part 1 - Placebo | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -50.5 mg/dL | Standard Deviation 70.47 |
| Part 1 - Placebo | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 330 | -37.2 mg/dL | Standard Deviation 123.09 |
| Part 1 - Placebo | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -27.9 mg/dL | Standard Deviation 115.46 |
| Part 1 - Placebo | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 510 | -20.9 mg/dL | Standard Deviation 118.05 |
| Part 1 - Placebo | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -43.5 mg/dL | Standard Deviation 92.99 |
| Part 1 - Placebo | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 270 | -27.3 mg/dL | Standard Deviation 154.94 |
| Part 1 - Inclisiran | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -11.0 mg/dL | Standard Deviation 124.27 |
| Part 1 - Inclisiran | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 270 | -17.5 mg/dL | Standard Deviation 85.85 |
| Part 1 - Inclisiran | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 330 | -17.9 mg/dL | Standard Deviation 113.1 |
| Part 1 - Inclisiran | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 450 | -19.8 mg/dL | Standard Deviation 111.41 |
| Part 1 - Inclisiran | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 510 | -2.2 mg/dL | Standard Deviation 127.13 |
| Part 1 - Inclisiran | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -14.9 mg/dL | Standard Deviation 107.9 |
| Part 1 - Inclisiran | Absolute Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -8.6 mg/dL | Standard Deviation 112.93 |
Secondary
Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180
Absolute change in non-HDL-C levels from Baseline to subsequent visits up to Day 180
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 90 | 3.8 mg/dL |
| Part 1 - Placebo | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 150 | -11.6 mg/dL |
| Part 1 - Placebo | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 180 | -5.7 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 90 | -15.3 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 150 | 0.6 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 180 | -12.7 mg/dL |
Comparison: Day 90p-value: 0.484895% CI: [-73.6, 35.3]Mixed Model Repeated Measures
Comparison: Day 150p-value: 0.72295% CI: [-56, 80.3]Mixed Model Repeated Measures
Comparison: Day 180p-value: 0.803695% CI: [-63.6, 49.5]Mixed Model Repeated Measures
Secondary
Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720
Absolute Change in non-HDL Cholesterol (non-HDL-C) from Baseline to Subsequent Visits up to Day 720
Time frame: Baseline, Days 270, 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.~.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -38.9 mg/dL | Standard Deviation 91.89 |
| Part 1 - Placebo | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 510 | -19.3 mg/dL | Standard Deviation 120.58 |
| Part 1 - Placebo | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -43.8 mg/dL | Standard Deviation 70.56 |
| Part 1 - Placebo | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -21.0 mg/dL | Standard Deviation 116.12 |
| Part 1 - Placebo | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 330 | -37.2 mg/dL | Standard Deviation 127.12 |
| Part 1 - Placebo | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 450 | -8.8 mg/dL | Standard Deviation 109.91 |
| Part 1 - Placebo | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 270 | -24.7 mg/dL | Standard Deviation 157.98 |
| Part 1 - Inclisiran | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 330 | -13.9 mg/dL | Standard Deviation 114.51 |
| Part 1 - Inclisiran | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 270 | -17.1 mg/dL | Standard Deviation 86.34 |
| Part 1 - Inclisiran | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 450 | -15.8 mg/dL | Standard Deviation 112.63 |
| Part 1 - Inclisiran | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -7.8 mg/dL | Standard Deviation 114.44 |
| Part 1 - Inclisiran | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 510 | -2.4 mg/dL | Standard Deviation 128.45 |
| Part 1 - Inclisiran | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -9.3 mg/dL | Standard Deviation 127.46 |
| Part 1 - Inclisiran | Absolute Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -14.7 mg/dL | Standard Deviation 112.04 |
Secondary
Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180
Absolute Change in PCSK9 from baseline to subsequent visits up to Day 180
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 | Day 90 | -25.8 ug/L |
| Part 1 - Placebo | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 | Day 150 | -30.7 ug/L |
| Part 1 - Placebo | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 | Day 180 | 88.8 ug/L |
| Part 1 - Inclisiran | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 | Day 90 | -342.5 ug/L |
| Part 1 - Inclisiran | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 | Day 150 | -335.2 ug/L |
| Part 1 - Inclisiran | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 | Day 180 | -301.5 ug/L |
Comparison: Day 90p-value: <0.000195% CI: [-420.7, -212.6]Mixed Model Repeated Measures
Comparison: Day 150p-value: <0.000195% CI: [-408, -200.8]Mixed Model Repeated Measures
Comparison: Day 180p-value: <0.000195% CI: [-504.5, -276.3]Mixed Model Repeated Measures
Secondary
Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720
Absolute Change in PCSK9 from baseline to subsequent visits up to Day 720
Time frame: Baseline, Days 270, 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 270 | -174.7 ug/L | Standard Deviation 252.1 |
| Part 1 - Placebo | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 450 | -237.5 ug/L | Standard Deviation 199.34 |
| Part 1 - Placebo | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 510 | -304.8 ug/L | Standard Deviation 181.41 |
| Part 1 - Placebo | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -243.6 ug/L | Standard Deviation 201.07 |
| Part 1 - Placebo | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -275.5 ug/L | Standard Deviation 163.85 |
| Part 1 - Placebo | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -296.8 ug/L | Standard Deviation 171.96 |
| Part 1 - Placebo | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 330 | -232.1 ug/L | Standard Deviation 193.51 |
| Part 1 - Inclisiran | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -303.1 ug/L | Standard Deviation 200.37 |
| Part 1 - Inclisiran | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 330 | -392.0 ug/L | Standard Deviation 422.93 |
| Part 1 - Inclisiran | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -413.2 ug/L | Standard Deviation 460.33 |
| Part 1 - Inclisiran | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 450 | -387.6 ug/L | Standard Deviation 483.81 |
| Part 1 - Inclisiran | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -441.8 ug/L | Standard Deviation 278.87 |
| Part 1 - Inclisiran | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 510 | -381.0 ug/L | Standard Deviation 261.04 |
| Part 1 - Inclisiran | Absolute Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 270 | -234.4 ug/L | Standard Deviation 242.25 |
Secondary
Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180
Absolute Change in total cholesterol from baseline to subsequent visits up to Day 180
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 | Day 150 | -10.5 mg/dL |
| Part 1 - Placebo | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 | Day 180 | -6.8 mg/dL |
| Part 1 - Placebo | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 | Day 90 | 3.9 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 | Day 90 | -15.1 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 | Day 150 | 0.6 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 | Day 180 | -12.6 mg/dL |
Comparison: Day 90p-value: 0.491195% CI: [-74, 36]Mixed Model Repeated Measures
Comparison: Day 150p-value: 0.746195% CI: [-57.2, 79.4]Mixed Model Repeated Measures
Comparison: Day 180p-value: 0.83795% CI: [-62.8, 51.1]Mixed Model Repeated Measures
Secondary
Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720
Absolute Change in total cholesterol from baseline to subsequent visits up to Day 720
Time frame: Baseline, Days 270, 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 450 | -7.9 mg/dL | Standard Deviation 107.22 |
| Part 1 - Placebo | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 630 | -44.5 mg/dL | Standard Deviation 71.81 |
| Part 1 - Placebo | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 330 | -35.6 mg/dL | Standard Deviation 127.19 |
| Part 1 - Placebo | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 690 | -21.6 mg/dL | Standard Deviation 118.21 |
| Part 1 - Placebo | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 510 | -17.8 mg/dL | Standard Deviation 120.4 |
| Part 1 - Placebo | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 720 | -40.4 mg/dL | Standard Deviation 93.21 |
| Part 1 - Placebo | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 270 | -24.9 mg/dL | Standard Deviation 154.6 |
| Part 1 - Inclisiran | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 720 | -8.5 mg/dL | Standard Deviation 126.48 |
| Part 1 - Inclisiran | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 270 | -13.3 mg/dL | Standard Deviation 90.68 |
| Part 1 - Inclisiran | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 330 | -13.0 mg/dL | Standard Deviation 115.59 |
| Part 1 - Inclisiran | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 450 | -14.4 mg/dL | Standard Deviation 113.71 |
| Part 1 - Inclisiran | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 510 | 0.1 mg/dL | Standard Deviation 128.73 |
| Part 1 - Inclisiran | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 630 | -14.9 mg/dL | Standard Deviation 111.5 |
| Part 1 - Inclisiran | Absolute Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 690 | -6.9 mg/dL | Standard Deviation 114.58 |
Secondary
Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720
Absolute change in VLDL-C levels from Baseline to Subsequent Visits up to Day 720
Time frame: Baseline, Days 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 330 | 0.0 mg/dL | Standard Deviation 9.38 |
| Part 1 - Placebo | Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 450 | 1.1 mg/dL | Standard Deviation 5.84 |
| Part 1 - Placebo | Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 510 | -0.9 mg/dL | Standard Deviation 4.76 |
| Part 1 - Placebo | Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 630 | 6.7 mg/dL | Standard Deviation 13.76 |
| Part 1 - Placebo | Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 690 | 6.9 mg/dL | Standard Deviation 14.58 |
| Part 1 - Placebo | Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 720 | 2.5 mg/dL | Standard Deviation 6.81 |
| Part 1 - Inclisiran | Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 690 | 0.8 mg/dL | Standard Deviation 9.34 |
| Part 1 - Inclisiran | Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 330 | 2.7 mg/dL | Standard Deviation 8.03 |
| Part 1 - Inclisiran | Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 630 | 0.2 mg/dL | Standard Deviation 8.39 |
| Part 1 - Inclisiran | Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 450 | 4.4 mg/dL | Standard Deviation 8.91 |
| Part 1 - Inclisiran | Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 720 | 1.7 mg/dL | Standard Deviation 9.06 |
| Part 1 - Inclisiran | Absolute Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 510 | -0.2 mg/dL | Standard Deviation 8.85 |
Secondary
Absolute Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180
Absolute Change in VLDL-C levels from baseline to subsequent visits on Days 90, 150, and 180
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Absolute Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 90 | 0.6 mg/dL |
| Part 1 - Placebo | Absolute Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 180 | 1.8 mg/dL |
| Part 1 - Placebo | Absolute Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 150 | 3.0 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 90 | 1.6 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 150 | 0.4 mg/dL |
| Part 1 - Inclisiran | Absolute Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 180 | 1.5 mg/dL |
Comparison: Day 90p-value: 0.649795% CI: [-3.2, 5.2]Mixed Model Repeated Measures
Comparison: Day 150p-value: 0.320995% CI: [-7.9, 2.6]Mixed Model Repeated Measures
Comparison: Day 180p-value: 0.929495% CI: [-6.3, 5.7]Mixed Model Repeated Measures
Secondary
Individual Responsiveness of Subjects: Part 1
Individual Responsiveness of Subjects defined as the number of subjects reaching on treatment LDL-C levels of \<25 mg/dL, \<50 mg/dL, \<70 mg/dL, and \<100 mg/dL up to Day 180
Time frame: Days 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 1 | <50 mg/dL- Day 150 | 1 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 1 | <50 mg/dL- Day 180 | 0 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 1 | <100 mg/dL- Day 150 | 1 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 1 | <70 mg/dL- Day 180 | 0 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 1 | >= 100 mg/dL- Day 150 | 17 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 1 | <100 mg/dL- Day 180 | 0 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 1 | <70 mg/dL- Day 150 | 1 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 1 | >= 100 mg/dL- Day 180 | 19 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 1 | <25 mg/dL- Day 180 | 0 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 1 | <25 mg/dL- Day 150 | 0 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 1 | <100 mg/dL- Day 150 | 5 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 1 | <25 mg/dL- Day 150 | 0 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 1 | <50 mg/dL- Day 150 | 0 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 1 | <70 mg/dL- Day 150 | 2 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 1 | >= 100 mg/dL- Day 150 | 29 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 1 | <25 mg/dL- Day 180 | 0 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 1 | <50 mg/dL- Day 180 | 1 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 1 | <70 mg/dL- Day 180 | 2 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 1 | <100 mg/dL- Day 180 | 5 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 1 | >= 100 mg/dL- Day 180 | 26 Participants |
Secondary
Individual Responsiveness of Subjects: Part 2
Individual Responsiveness of Subjects defined as the number of subjects reaching on treatment LDL-C levels of \<25 mg/dL, \<50 mg/dL, \<70 mg/dL, and \<100 mg/dL up to Day 720
Time frame: Days 330, 510, 690 and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | >= 100 mg/dL- Day 330 | 14 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | <25 mg/dL- Day 330 | 0 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | <25 mg/dL- Day 690 | 0 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | <50 mg/dL- Day 330 | 1 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | <100 mg/dL- Day 330 | 2 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | <25 mg/dL- Day 510 | 0 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | >= 100 mg/dL- Day 690 | 13 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | <50 mg/dL- Day 510 | 0 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | < 100 mg/dL- Day 510 | 1 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | <70 mg/dL- Day 510 | 0 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | <50 mg/dL- Day 690 | 0 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | <25 mg/dL- Day 720 | 0 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | <70 mg/dL- Day 690 | 0 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | <70 mg/dL- Day 330 | 2 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | <100 mg/dL- Day 690 | 1 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | <50 mg/dL- Day 720 | 0 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | >= 100 mg/dL- Day 510 | 16 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | <100 mg/dL- Day 720 | 1 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | <70 mg/dL- Day 720 | 1 Participants |
| Part 1 - Placebo | Individual Responsiveness of Subjects: Part 2 | >= 100 mg/dL- Day 720 | 17 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | >= 100 mg/dL- Day 720 | 22 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | <70 mg/dL- Day 330 | 1 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | <100 mg/dL- Day 330 | 5 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | <70 mg/dL- Day 510 | 3 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | < 100 mg/dL- Day 510 | 5 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | >= 100 mg/dL- Day 510 | 25 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | <25 mg/dL- Day 690 | 0 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | >= 100 mg/dL- Day 690 | 20 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | <25 mg/dL- Day 720 | 0 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | <50 mg/dL- Day 720 | 1 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | <50 mg/dL- Day 330 | 0 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | <25 mg/dL- Day 330 | 0 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | >= 100 mg/dL- Day 330 | 20 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | <25 mg/dL- Day 510 | 0 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | <50 mg/dL- Day 510 | 2 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | <50 mg/dL- Day 690 | 0 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | <70 mg/dL- Day 690 | 1 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | <100 mg/dL- Day 690 | 2 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | <70 mg/dL- Day 720 | 1 Participants |
| Part 1 - Inclisiran | Individual Responsiveness of Subjects: Part 2 | <100 mg/dL- Day 720 | 5 Participants |
Secondary
LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1
Proportion of subjects in each group with ≥20% or ≥30% LDL-C reduction from Baseline in Part 1 (Days 90, 150, 180)
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 - Placebo | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 | LDL-C >=20%: Day 90 | 4 Participants |
| Part 1 - Placebo | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 | LDL-C >=20%: Day 150 | 3 Participants |
| Part 1 - Placebo | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 | LDL-C >=20%: Day 180 | 3 Participants |
| Part 1 - Placebo | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 | LDL-C >=30%: Day 150 | 3 Participants |
| Part 1 - Placebo | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 | LDL-C >=30%: Day 180 | 2 Participants |
| Part 1 - Placebo | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 | LDL-C >=30%: Day 90 | 3 Participants |
| Part 1 - Inclisiran | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 | LDL-C >=30%: Day 180 | 10 Participants |
| Part 1 - Inclisiran | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 | LDL-C >=20%: Day 90 | 14 Participants |
| Part 1 - Inclisiran | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 | LDL-C >=30%: Day 150 | 6 Participants |
| Part 1 - Inclisiran | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 | LDL-C >=20%: Day 150 | 9 Participants |
| Part 1 - Inclisiran | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 | LDL-C >=30%: Day 90 | 13 Participants |
| Part 1 - Inclisiran | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 1 | LDL-C >=20%: Day 180 | 12 Participants |
Secondary
LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2
Proportion of subjects in each group with ≥20% or ≥30% LDL-C reduction from Baseline in Part 2 (Days 330, 510, 690, and 720)
Time frame: Baseline, Days 330, 510, 690, and 720
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 - Placebo | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 | LDL-C >=20%: Day 330 | 5 Participants |
| Part 1 - Placebo | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 | LDL-C >=20%: Day 510 | 6 Participants |
| Part 1 - Placebo | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 | LDL-C >=20%: Day 690 | 8 Participants |
| Part 1 - Placebo | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 | LDL-C >=20%: Day 720 | 7 Participants |
| Part 1 - Placebo | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 | LDL-C >=30%: Day 330 | 4 Participants |
| Part 1 - Placebo | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 | LDL-C >=30%: Day 510 | 4 Participants |
| Part 1 - Placebo | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 | LDL-C >=30%: Day 690 | 4 Participants |
| Part 1 - Placebo | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 | LDL-C >=30%: Day 720 | 5 Participants |
| Part 1 - Inclisiran | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 | LDL-C >=30%: Day 720 | 8 Participants |
| Part 1 - Inclisiran | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 | LDL-C >=20%: Day 330 | 13 Participants |
| Part 1 - Inclisiran | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 | LDL-C >=30%: Day 330 | 8 Participants |
| Part 1 - Inclisiran | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 | LDL-C >=20%: Day 510 | 11 Participants |
| Part 1 - Inclisiran | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 | LDL-C >=30%: Day 690 | 5 Participants |
| Part 1 - Inclisiran | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 | LDL-C >=20%: Day 690 | 11 Participants |
| Part 1 - Inclisiran | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 | LDL-C >=30%: Day 510 | 9 Participants |
| Part 1 - Inclisiran | LDL-C Reduction ≥20% or ≥30% From Baseline: Part 2 | LDL-C >=20%: Day 720 | 13 Participants |
Secondary
Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720
Percentage change in Apolipoprotein A-1 (Apo-A1) from Baseline to Subsequent Visits up to Day 720
Time frame: Baseline, Days 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 330 | 0.4 Percentage change | Standard Deviation 11.37 |
| Part 1 - Placebo | Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 450 | 4.4 Percentage change | Standard Deviation 10.76 |
| Part 1 - Placebo | Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 510 | 6.2 Percentage change | Standard Deviation 17 |
| Part 1 - Placebo | Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 630 | 5.4 Percentage change | Standard Deviation 11.11 |
| Part 1 - Placebo | Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 690 | 5.6 Percentage change | Standard Deviation 13.92 |
| Part 1 - Placebo | Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 720 | 3.5 Percentage change | Standard Deviation 11.71 |
| Part 1 - Inclisiran | Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 630 | 0.8 Percentage change | Standard Deviation 9.93 |
| Part 1 - Inclisiran | Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 720 | 5.5 Percentage change | Standard Deviation 9.27 |
| Part 1 - Inclisiran | Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 450 | 3.9 Percentage change | Standard Deviation 12.71 |
| Part 1 - Inclisiran | Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 330 | 1.3 Percentage change | Standard Deviation 10.8 |
| Part 1 - Inclisiran | Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 510 | 6.8 Percentage change | Standard Deviation 13.4 |
| Part 1 - Inclisiran | Percent Change Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 720 | Day 690 | 7.2 Percentage change | Standard Deviation 12.17 |
Secondary
Percent Change in Apo-B From Baseline to Day 150
Percentage change in Apo-B from baseline to Day 150 as demonstrated using the ANCOVA statisitical model.
Time frame: Baseline, Day 150
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1 - Placebo | Percent Change in Apo-B From Baseline to Day 150 | 3.55 Percentage change |
| Part 1 - Inclisiran | Percent Change in Apo-B From Baseline to Day 150 | -0.75 Percentage change |
p-value: 0.681495% CI: [-24.88, 16.27]ANCOVA
Secondary
Percent Change in Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 180
Percentage Change in Apolipoprotein A-1 (Apo-A1) from baseline to subsequent visits on Day 90, 150, and 180
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Percent Change in Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 180 | Day 90 | 1.6 Percentage change |
| Part 1 - Placebo | Percent Change in Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 180 | Day 180 | 1.6 Percentage change |
| Part 1 - Placebo | Percent Change in Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 180 | Day 150 | 3.0 Percentage change |
| Part 1 - Inclisiran | Percent Change in Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 180 | Day 180 | -1.0 Percentage change |
| Part 1 - Inclisiran | Percent Change in Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 180 | Day 90 | 0.6 Percentage change |
| Part 1 - Inclisiran | Percent Change in Apolipoprotein A-1 (Apo-A1) From Baseline to Subsequent Visits up to Day 180 | Day 150 | 0.4 Percentage change |
Comparison: Day 90p-value: 0.795895% CI: [-8.4, 6.5]Mixed Model Repeated Measures
Comparison: Day 150p-value: 0.600395% CI: [-12.7, 7.4]Mixed Model Repeated Measures
Comparison: Day 180p-value: 0.535295% CI: [-11, 5.8]Mixed Model Repeated Measures
Secondary
Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180
Percentage change in Apolipoprotein B (apoB) from baseline to subsequent visits up to Day 180 demonstrated by Mixed Model Repeated Measures statisitical method.
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 | Day 150 | 2.8 Percentage change |
| Part 1 - Placebo | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 | Day 180 | 4.5 Percentage change |
| Part 1 - Placebo | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 | Day 90 | 6.3 Percentage change |
| Part 1 - Inclisiran | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 | Day 90 | -6.4 Percentage change |
| Part 1 - Inclisiran | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 | Day 150 | -0.7 Percentage change |
| Part 1 - Inclisiran | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 180 | Day 180 | -5.8 Percentage change |
Comparison: Day 90p-value: 0.137195% CI: [-29.5, 4.2]Mixed Model Repeated Measures
Comparison: Day 150p-value: 0.7195% CI: [-22.6, 15.5]Mixed Model Repeated Measures
Comparison: Day 180p-value: 0.227895% CI: [-27.2, 6.6]Mixed Model Repeated Measures
Secondary
Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720
Percentage Change in Apolipoprotein B (apoB) from baseline to subsequent visits up to Day 720
Time frame: Baseline, Days 270, 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 | Day 450 | -1.3 Percentage Change | Standard Deviation 21.62 |
| Part 1 - Placebo | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -7.3 Percentage Change | Standard Deviation 17.81 |
| Part 1 - Placebo | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 | Day 330 | -7.9 Percentage Change | Standard Deviation 28.56 |
| Part 1 - Placebo | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -3.7 Percentage Change | Standard Deviation 27.16 |
| Part 1 - Placebo | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 | Day 510 | -3.7 Percentage Change | Standard Deviation 24.21 |
| Part 1 - Placebo | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -10.4 Percentage Change | Standard Deviation 19.68 |
| Part 1 - Placebo | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 | Day 270 | -0.6 Percentage Change | Standard Deviation 40.91 |
| Part 1 - Inclisiran | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -8.0 Percentage Change | Standard Deviation 31.93 |
| Part 1 - Inclisiran | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 | Day 270 | -3.3 Percentage Change | Standard Deviation 28.67 |
| Part 1 - Inclisiran | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 | Day 330 | -3.6 Percentage Change | Standard Deviation 34.35 |
| Part 1 - Inclisiran | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 | Day 450 | -3.5 Percentage Change | Standard Deviation 35.66 |
| Part 1 - Inclisiran | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 | Day 510 | 1.9 Percentage Change | Standard Deviation 44.49 |
| Part 1 - Inclisiran | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -6.6 Percentage Change | Standard Deviation 32.97 |
| Part 1 - Inclisiran | Percent Change in Apolipoprotein B (apoB) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -5.8 Percentage Change | Standard Deviation 32.38 |
Secondary
Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180
Percentage Change in HDL-C levels (mg/dL) from baseline to subsequent visits on Day 90, 150, and 180
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 90 | -1.1 Percentage change |
| Part 1 - Placebo | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 150 | 2.3 Percentage change |
| Part 1 - Placebo | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 180 | -1.9 Percentage change |
| Part 1 - Inclisiran | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 90 | 1.4 Percentage change |
| Part 1 - Inclisiran | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 150 | 3.6 Percentage change |
| Part 1 - Inclisiran | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 180 | 1.5 Percentage change |
Comparison: Day 90p-value: 0.602895% CI: [-6.8, 11.7]Mixed Model Repeated Measures
Comparison: Day 150p-value: 0.842895% CI: [-11.5, 14]Mixed Model Repeated Measures
Comparison: Day 180p-value: 0.494695% CI: [-6.6, 13.4]Mixed Model Repeated Measures
Secondary
Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720
Percentage change in LDL-C levels from Baseline to Subsequent Visits up to Day 720
Time frame: Baseline, Days 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 330 | 3.2 Percentage change | Standard Deviation 13.09 |
| Part 1 - Placebo | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 450 | 1.6 Percentage change | Standard Deviation 12.26 |
| Part 1 - Placebo | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 510 | 2.9 Percentage change | Standard Deviation 19.83 |
| Part 1 - Placebo | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -2.0 Percentage change | Standard Deviation 14.81 |
| Part 1 - Placebo | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -2.4 Percentage change | Standard Deviation 19.17 |
| Part 1 - Placebo | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -3.6 Percentage change | Standard Deviation 14.9 |
| Part 1 - Inclisiran | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 690 | 4.5 Percentage change | Standard Deviation 20.31 |
| Part 1 - Inclisiran | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 330 | 4.3 Percentage change | Standard Deviation 16.45 |
| Part 1 - Inclisiran | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 630 | 0.5 Percentage change | Standard Deviation 15.81 |
| Part 1 - Inclisiran | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 450 | 4.8 Percentage change | Standard Deviation 17.81 |
| Part 1 - Inclisiran | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 720 | 4.1 Percentage change | Standard Deviation 16.99 |
| Part 1 - Inclisiran | Percent Change in High-Density Lipoprotein Cholesterol Levels (HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 510 | 7.9 Percentage change | Standard Deviation 17.75 |
Secondary
Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1
Percent change in hsCRP from Baseline to subsequent visits up to Day 180
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population (Part 1): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 | Day 90 | 41.2 Percentage Change | Standard Deviation 243.94 |
| Part 1 - Placebo | Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 | Day 150 | 230.8 Percentage Change | Standard Deviation 640.11 |
| Part 1 - Placebo | Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 | Day 180 | 115.1 Percentage Change | Standard Deviation 490.17 |
| Part 1 - Inclisiran | Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 | Day 90 | 42.0 Percentage Change | Standard Deviation 170.41 |
| Part 1 - Inclisiran | Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 | Day 150 | 126.9 Percentage Change | Standard Deviation 380.15 |
| Part 1 - Inclisiran | Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 180: Part 1 | Day 180 | 45.2 Percentage Change | Standard Deviation 143.24 |
Secondary
Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2
Percentage change in hsCRP from baseline to subsequent visits up to Day 720
Time frame: Baseline, Days 330, 510 ,690, 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Day 330 | 178.9 Percentage Change | Standard Deviation 657.67 |
| Part 1 - Placebo | Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Day 510 | 266.7 Percentage Change | Standard Deviation 936.76 |
| Part 1 - Placebo | Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Day 690 | 29.0 Percentage Change | Standard Deviation 125.18 |
| Part 1 - Placebo | Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Day 720 | 49.6 Percentage Change | Standard Deviation 167.16 |
| Part 1 - Inclisiran | Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Day 720 | 38.60 Percentage Change | Standard Deviation 112.57 |
| Part 1 - Inclisiran | Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Day 330 | 17.3 Percentage Change | Standard Deviation 73.29 |
| Part 1 - Inclisiran | Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Day 690 | 37.5 Percentage Change | Standard Deviation 92.4 |
| Part 1 - Inclisiran | Percent Change in High-Sensitivity C-Reactive Protein (hsCRP) From Baseline to Subsequent Visits up to Day 720: Part 2 | Day 510 | 64.7 Percentage Change | Standard Deviation 204.54 |
Secondary
Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180
Percentage Change in Lp(a) from Baseline to Subsequent Visits up to Day 180
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 | Day 90 | 4.3 Percentage change |
| Part 1 - Placebo | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 | Day 150 | 15.2 Percentage change |
| Part 1 - Placebo | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 | Day 180 | 4.9 Percentage change |
| Part 1 - Inclisiran | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 | Day 90 | -4.6 Percentage change |
| Part 1 - Inclisiran | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 | Day 150 | -3.8 Percentage change |
| Part 1 - Inclisiran | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 180 | Day 180 | -4.8 Percentage change |
Comparison: Day 90p-value: 0.171695% CI: [-21.8, 4]Mixed Model Repeated Measures
Comparison: Day 150p-value: 0.167195% CI: [-46.2, 8.2]Mixed Model Repeated Measures
Comparison: Day 180p-value: 0.180895% CI: [-24.2, 4.7]Mixed Model Repeated Measures
Secondary
Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720
Percentage change in Lp(a) from Baseline to Subsequent Visits up to Day 720
Time frame: Baseline, Days 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 330 | 2.5 Percentage change | Standard Deviation 33.15 |
| Part 1 - Placebo | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 510 | 8.3 Percentage change | Standard Deviation 44.74 |
| Part 1 - Placebo | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 720 | -11.4 Percentage change | Standard Deviation 51.06 |
| Part 1 - Placebo | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 630 | -8.4 Percentage change | Standard Deviation 32.65 |
| Part 1 - Placebo | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 450 | 3.4 Percentage change | Standard Deviation 45.12 |
| Part 1 - Placebo | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 690 | -10.7 Percentage change | Standard Deviation 34.02 |
| Part 1 - Inclisiran | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 450 | 0.2 Percentage change | Standard Deviation 26.42 |
| Part 1 - Inclisiran | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 720 | -3.1 Percentage change | Standard Deviation 45.08 |
| Part 1 - Inclisiran | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 330 | -1.4 Percentage change | Standard Deviation 26.69 |
| Part 1 - Inclisiran | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 690 | -5.3 Percentage change | Standard Deviation 27.44 |
| Part 1 - Inclisiran | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 510 | 13.4 Percentage change | Standard Deviation 39.37 |
| Part 1 - Inclisiran | Percent Change in Lipoprotein(a) [Lp(a)] From Baseline to Subsequent Visits up to Day 720 | Day 630 | 1.7 Percentage change | Standard Deviation 29.43 |
Secondary
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180
Percentage Change in LDL-C levels from baseline to subsequent visits on Days 90, 150, and 180
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 90 | 3.3 Percentage change |
| Part 1 - Placebo | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 150 | -2.9 Percentage change |
| Part 1 - Placebo | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 180 | -1.5 Percentage change |
| Part 1 - Inclisiran | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 90 | -8.7 Percentage change |
| Part 1 - Inclisiran | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 150 | 1.8 Percentage change |
| Part 1 - Inclisiran | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 180 | -7.2 Percentage change |
Comparison: Day 90p-value: 0.234795% CI: [-32.2, 8.1]Mixed Model Repeated Measures
Comparison: Day 150p-value: 0.705895% CI: [-19.9, 29.2]Mixed Model Repeated Measures
Comparison: Day 180p-value: 0.565395% CI: [-25.5, 14.1]Mixed Model Repeated Measures
Secondary
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720
Percentage Change in LDL-C levels from baseline to subsequent visits up to Day 720
Time frame: Baseline, Days 270, 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 270 | -10.1 Percentage change | Standard Deviation 41.62 |
| Part 1 - Placebo | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -16.6 Percentage change | Standard Deviation 20.45 |
| Part 1 - Placebo | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 330 | -14.4 Percentage change | Standard Deviation 32.62 |
| Part 1 - Placebo | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -8.7 Percentage change | Standard Deviation 32.17 |
| Part 1 - Placebo | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 510 | -9.3 Percentage change | Standard Deviation 29.52 |
| Part 1 - Placebo | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -14.6 Percentage change | Standard Deviation 26.11 |
| Part 1 - Placebo | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 450 | -6.7 Percentage change | Standard Deviation 26.69 |
| Part 1 - Inclisiran | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -6.2 Percentage change | Standard Deviation 47.29 |
| Part 1 - Inclisiran | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 330 | -4.8 Percentage change | Standard Deviation 50.45 |
| Part 1 - Inclisiran | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 450 | -4.7 Percentage change | Standard Deviation 46.92 |
| Part 1 - Inclisiran | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 510 | 2.4 Percentage change | Standard Deviation 61.7 |
| Part 1 - Inclisiran | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -6.6 Percentage change | Standard Deviation 43.75 |
| Part 1 - Inclisiran | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -4.2 Percentage change | Standard Deviation 42.39 |
| Part 1 - Inclisiran | Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 270 | -9.1 Percentage change | Standard Deviation 33.99 |
Secondary
Percent Change in Non-HDL-C From Baseline to Day 150
Percentage Change in non-HDL-C from baseline to Day 150 as demonstrated using the ANCOVA statisitical model.
Time frame: Baseline, Day 150
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1 - Placebo | Percent Change in Non-HDL-C From Baseline to Day 150 | 2.46 Percentage Change |
| Part 1 - Inclisiran | Percent Change in Non-HDL-C From Baseline to Day 150 | 0.37 Percentage Change |
p-value: 0.872595% CI: [-27.7, 23.51]ANCOVA
Secondary
Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180
Percentage change in non-HDL-C levels from baseline to subsequent visits up to Day 180
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 90 | 2.9 Percentage change |
| Part 1 - Placebo | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 150 | -1.7 Percentage change |
| Part 1 - Placebo | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 180 | -1.1 Percentage change |
| Part 1 - Inclisiran | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 90 | -7.2 Percentage change |
| Part 1 - Inclisiran | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 150 | 1.3 Percentage change |
| Part 1 - Inclisiran | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 180 | -6.2 Percentage change |
Comparison: Day 90p-value: 0.287795% CI: [-29, 8.8]Mixed Model Repeated Measures
Comparison: Day 150p-value: 0.794495% CI: [-19.7, 25.7]Mixed Model Repeated Measures
Comparison: Day 180p-value: 0.580395% CI: [-23.4, 13.3]Mixed Model Repeated Measures
Secondary
Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720
Percentage Change in non-HDL-C from Baseline to subsequent visits up to Day 720
Time frame: Baseline, Days 270, 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 450 | -5.5 Percentage Change | Standard Deviation 25.49 |
| Part 1 - Placebo | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -13.6 Percentage Change | Standard Deviation 18.88 |
| Part 1 - Placebo | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 330 | -13.1 Percentage Change | Standard Deviation 31.27 |
| Part 1 - Placebo | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -6.4 Percentage Change | Standard Deviation 30.12 |
| Part 1 - Placebo | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 510 | -8.0 Percentage Change | Standard Deviation 28 |
| Part 1 - Placebo | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -12.3 Percentage Change | Standard Deviation 23.99 |
| Part 1 - Placebo | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 270 | -8.4 Percentage Change | Standard Deviation 39.76 |
| Part 1 - Inclisiran | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -5.0 Percentage Change | Standard Deviation 43.4 |
| Part 1 - Inclisiran | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 270 | -7.6 Percentage Change | Standard Deviation 30.95 |
| Part 1 - Inclisiran | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 330 | -2.3 Percentage Change | Standard Deviation 45.56 |
| Part 1 - Inclisiran | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 450 | -3.1 Percentage Change | Standard Deviation 43.73 |
| Part 1 - Inclisiran | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 510 | 2.0 Percentage Change | Standard Deviation 55.28 |
| Part 1 - Inclisiran | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -6.5 Percentage Change | Standard Deviation 40.16 |
| Part 1 - Inclisiran | Percent Change in Non-HDL Cholesterol (Non-HDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -3.6 Percentage Change | Standard Deviation 40.11 |
Secondary
Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180
Percentage Change in PCSK9 from baseline to subsequent visits up to Day 180
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 | Day 90 | 9.1 Percentage change |
| Part 1 - Placebo | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 | Day 150 | 4.1 Percentage change |
| Part 1 - Placebo | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 | Day 180 | 39.2 Percentage change |
| Part 1 - Inclisiran | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 | Day 90 | -53.5 Percentage change |
| Part 1 - Inclisiran | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 | Day 150 | -56.5 Percentage change |
| Part 1 - Inclisiran | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 180 | Day 180 | -53.1 Percentage change |
Comparison: Day 90p-value: <0.000195% CI: [-80.1, -45.1]Mixed Model Repeated Measures
Comparison: Day 150p-value: <0.000195% CI: [-83.5, -37.8]Mixed Model Repeated Measures
Comparison: Day 150p-value: <0.000195% CI: [-120.4, -64.2]Mixed Model Repeated Measures
Secondary
Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720
Percentage Change in PCSK9 from baseline to subsequent visits up to Day 720
Time frame: Baseline, Days 270, 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -48.3 Percentage Change | Standard Deviation 22.3 |
| Part 1 - Placebo | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 330 | -42.6 Percentage Change | Standard Deviation 32.08 |
| Part 1 - Placebo | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -53.8 Percentage Change | Standard Deviation 16.66 |
| Part 1 - Placebo | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 450 | -35.8 Percentage Change | Standard Deviation 37.55 |
| Part 1 - Placebo | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 510 | -54.0 Percentage Change | Standard Deviation 23.62 |
| Part 1 - Placebo | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -41.7 Percentage Change | Standard Deviation 29.19 |
| Part 1 - Placebo | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 270 | -21.5 Percentage Change | Standard Deviation 55.71 |
| Part 1 - Inclisiran | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 510 | -59.4 Percentage Change | Standard Deviation 24.13 |
| Part 1 - Inclisiran | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 270 | -14.4 Percentage Change | Standard Deviation 160.6 |
| Part 1 - Inclisiran | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 450 | -51.1 Percentage Change | Standard Deviation 27.9 |
| Part 1 - Inclisiran | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 690 | -64.3 Percentage Change | Standard Deviation 11.21 |
| Part 1 - Inclisiran | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 630 | -48.1 Percentage Change | Standard Deviation 32.65 |
| Part 1 - Inclisiran | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 720 | -57.6 Percentage Change | Standard Deviation 39.76 |
| Part 1 - Inclisiran | Percent Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Subsequent Visits up to Day 720 | Day 330 | -57.0 Percentage Change | Standard Deviation 30.36 |
Secondary
Percent Change in Total Cholesterol From Baseline to Day 150
Percentage change in total cholesterol from baseline to Day 150 as demonstrated using the ANCOVA statisitical model.
Time frame: Baseline, Day 150
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1 - Placebo | Percent Change in Total Cholesterol From Baseline to Day 150 | 1.51 Percentage Change |
| Part 1 - Inclisiran | Percent Change in Total Cholesterol From Baseline to Day 150 | 0.71 Percentage Change |
p-value: 0.942595% CI: [-22.3, 20.72]ANCOVA
Secondary
Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180
Percentage change in total cholesterol from baseline to subsequent visits up to Day 180
Time frame: Baseline, Days 90, 150 and 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 | Day 90 | 2.0 Percentage Change |
| Part 1 - Placebo | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 | Day 150 | -1.5 Percentage Change |
| Part 1 - Placebo | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 | Day 180 | -1.4 Percentage Change |
| Part 1 - Inclisiran | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 | Day 90 | -5.9 Percentage Change |
| Part 1 - Inclisiran | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 | Day 150 | 1.2 Percentage Change |
| Part 1 - Inclisiran | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 180 | Day 180 | -4.9 Percentage Change |
Comparison: Day 90p-value: 0.329995% CI: [-23.9, 8.2]Mixed Model Repeated Measures
Comparison: Day 150p-value: 0.777895% CI: [-16.7, 22.2]Mixed Model Repeated Measures
Comparison: Day 180p-value: 0.661395% CI: [-19.2, 12.3]Mixed Model Repeated Measures
Secondary
Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720
Percentage change in total cholesterol from baseline to subsequent visits up to Day 720
Time frame: Baseline, Days 270, 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 450 | -4.2 Percentage Change | Standard Deviation 22.45 |
| Part 1 - Placebo | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 630 | -11.9 Percentage Change | Standard Deviation 17.58 |
| Part 1 - Placebo | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 330 | -10.9 Percentage Change | Standard Deviation 27.67 |
| Part 1 - Placebo | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 690 | -6.2 Percentage Change | Standard Deviation 26.71 |
| Part 1 - Placebo | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 510 | -6.4 Percentage Change | Standard Deviation 25.37 |
| Part 1 - Placebo | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 720 | -11.2 Percentage Change | Standard Deviation 21.86 |
| Part 1 - Placebo | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 270 | -7.4 Percentage Change | Standard Deviation 34.8 |
| Part 1 - Inclisiran | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 720 | -2.9 Percentage Change | Standard Deviation 36.7 |
| Part 1 - Inclisiran | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 270 | -4.8 Percentage Change | Standard Deviation 27.31 |
| Part 1 - Inclisiran | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 330 | -1.0 Percentage Change | Standard Deviation 39.2 |
| Part 1 - Inclisiran | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 450 | -2.2 Percentage Change | Standard Deviation 36.05 |
| Part 1 - Inclisiran | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 510 | 2.8 Percentage Change | Standard Deviation 46.77 |
| Part 1 - Inclisiran | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 630 | -4.8 Percentage Change | Standard Deviation 33.84 |
| Part 1 - Inclisiran | Percent Change in Total Cholesterol From Baseline to Subsequent Visits up to Day 720 | Day 690 | -1.9 Percentage Change | Standard Deviation 33.83 |
Secondary
Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720
Percentage change in VLDL-C levels from Baseline to Subsequent Visits up to Day 720
Time frame: Baseline, Days 330, 450, 510, 630, 690, and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 - Placebo | Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 330 | 6.8 Percentage Change | Standard Deviation 38.92 |
| Part 1 - Placebo | Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 450 | 7.1 Percentage Change | Standard Deviation 28.86 |
| Part 1 - Placebo | Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 510 | 2.1 Percentage Change | Standard Deviation 33.45 |
| Part 1 - Placebo | Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 630 | 25.1 Percentage Change | Standard Deviation 44.22 |
| Part 1 - Placebo | Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 690 | 26.5 Percentage Change | Standard Deviation 51.79 |
| Part 1 - Placebo | Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 720 | 13.9 Percentage Change | Standard Deviation 33.26 |
| Part 1 - Inclisiran | Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 690 | 11.4 Percentage Change | Standard Deviation 59.86 |
| Part 1 - Inclisiran | Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 330 | 20.8 Percentage Change | Standard Deviation 57.44 |
| Part 1 - Inclisiran | Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 630 | 6.2 Percentage Change | Standard Deviation 46.21 |
| Part 1 - Inclisiran | Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 450 | 23.9 Percentage Change | Standard Deviation 46.36 |
| Part 1 - Inclisiran | Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 720 | 12.4 Percentage Change | Standard Deviation 50.37 |
| Part 1 - Inclisiran | Percent Change in Very-Low-Density-Lipoprotein Cholesterol Levels (VLDL-C) From Baseline to Subsequent Visits up to Day 720 | Day 510 | 7.1 Percentage Change | Standard Deviation 43.16 |
Secondary
Percent Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180
Percentage Change in VLDL-C levels (mg/dL) from baseline to subsequent visits on Days 90, 150, and 180
Time frame: Baseline, Days 90, 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part 1 - Placebo | Percent Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 90 | 0.6 Percentage change |
| Part 1 - Placebo | Percent Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 150 | 16.3 Percentage change |
| Part 1 - Placebo | Percent Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 180 | 10.0 Percentage change |
| Part 1 - Inclisiran | Percent Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 90 | 11.9 Percentage change |
| Part 1 - Inclisiran | Percent Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 150 | 4.9 Percentage change |
| Part 1 - Inclisiran | Percent Change in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) From Baseline to Subsequent Visits up to Day 180 | Day 180 | 12.3 Percentage change |
Comparison: Day 90p-value: 0.310595% CI: [-10.8, 33.4]Mixed Model Repeated Measures
Comparison: Day 150p-value: 0.301895% CI: [-33.3, 10.5]Mixed Model Repeated Measures
Comparison: Day 180p-value: 0.875595% CI: [-27, 31.6]Mixed Model Repeated Measures
Secondary
Proportional Responsiveness of Subjects: Part 2
Number of participants in each group who attain global lipid targets for their indication
Time frame: Days 330, 510, 690 and 720
Population: ITT Population (Part 2): The overall number of participants analyzed represents the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 - Placebo | Proportional Responsiveness of Subjects: Part 2 | Day 330 | 2 Participants |
| Part 1 - Placebo | Proportional Responsiveness of Subjects: Part 2 | Day 690 | 0 Participants |
| Part 1 - Placebo | Proportional Responsiveness of Subjects: Part 2 | Day 510 | 0 Participants |
| Part 1 - Placebo | Proportional Responsiveness of Subjects: Part 2 | Day 720 | 1 Participants |
| Part 1 - Inclisiran | Proportional Responsiveness of Subjects: Part 2 | Day 510 | 4 Participants |
| Part 1 - Inclisiran | Proportional Responsiveness of Subjects: Part 2 | Day 330 | 2 Participants |
| Part 1 - Inclisiran | Proportional Responsiveness of Subjects: Part 2 | Day 720 | 2 Participants |
| Part 1 - Inclisiran | Proportional Responsiveness of Subjects: Part 2 | Day 690 | 1 Participants |
Secondary
Proportional Responsiveness: Part 1
Number of participants in each group who attain global lipid targets for their indication
Time frame: Days 150, 180
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population. The number analyzed per row represents participants with data at each time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 - Placebo | Proportional Responsiveness: Part 1 | Day 150 | 1 Participants |
| Part 1 - Placebo | Proportional Responsiveness: Part 1 | Day 180 | 0 Participants |
| Part 1 - Inclisiran | Proportional Responsiveness: Part 1 | Day 150 | 3 Participants |
| Part 1 - Inclisiran | Proportional Responsiveness: Part 1 | Day 180 | 3 Participants |
Secondary
Proportion of Subjects With ≥30% LDL-C Reduction of From Baseline at Day 150
Number of participants in each group with ≥30% LDL-C reduction from baseline at Day 150 using the Regression Logistic Statistical Model
Time frame: Baseline, Day 150
Population: ITT Population: All participants randomized into the study comprised the intent-to-treat (ITT) population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 - Placebo | Proportion of Subjects With ≥30% LDL-C Reduction of From Baseline at Day 150 | 3 Participants |
| Part 1 - Inclisiran | Proportion of Subjects With ≥30% LDL-C Reduction of From Baseline at Day 150 | 6 Participants |
95% CI: [0.2, 5.2]Regression, Logistic