Hypercholesterolemia
Conditions
Keywords
low density lipoprotein, heterozygous familial hypercholesterolemia, polygenic hypercholesterolemia
Brief summary
This study is designed to define the amount and duration of cholesterol lowering and to assess the safety and tolerability of different dose regimens of LY3015014 in participants with high cholesterol. The study will also investigate how the body processes the drug and how the drug affects the body. Participants will remain on a stable diet and will continue taking cholesterol-lowering medications (statins with or without ezetimibe). After signing the informed consent document, the participant will complete a screening/run-in period that will last at most 8 weeks. Then, the treatment period will last approximately 16 weeks. After the treatment period, the participants will complete a follow-up period lasting approximately 8 weeks for a total study duration ranging from approximately 25 to 32 weeks.
Interventions
DRUGLY3015014
Administered SC
DRUGPlacebo
Administered SC
DRUGStatin
Administered orally
DRUGEzetimibe
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with high low density lipoprotein (LDL) cholesterol * Are on stable daily dose of a statin or have a history of statin intolerance * Men with a partner who can become pregnant must agree to use barrier protection during sexual intercourse to prevent pregnancies * Women who cannot become pregnant, or women who are not pregnant or breast feeding and agree to use a reliable method of birth control to prevent pregnancies
Exclusion criteria
* Have high cholesterol due to another disease or have a rare and serious form of hereditary high cholesterol * Have had recent heart attack, stroke, blood clot or heart surgery, have planned heart or blood vessel surgery, or has a heart that does not pump sufficiently well * Have poorly controlled high blood pressure * Have diabetes that requires an injectable medication (including insulin), or have diabetes that is poorly controlled * Have thyroid blood test that is outside normal range * Have a history of adrenal gland disorder * Have a history of vitamin E deficiency or fat malabsorption syndrome * Have poor kidney function * Have active liver or gall bladder disease, history of hepatitis or liver blood tests that are high * Have a history of muscle disease including muscle damage from a medicine or muscle blood test that is high * Are anemic (low red blood cell counts) * Have a history of allergy or intolerance to other antibody medications * Have a history of human immunodeficiency virus infection (HIV) infection * Are likely to have a major operation or be hospitalized during the study * Have chronic alcohol or drug abuse or dependency * Have or suspected to have any cancer or malignant tumor * Have an active serious infection * Have started or stopped taking a statin or ezetimibe medication, or changed statin dose regimen recently * Are on a statin regimen other than daily dosing (for example, an every-other-day statin regimen) * Have recently used simvastatin (highest dose level), fibrates, bile acid binders, niacin, probucol, or over-the-counter/health food preparations to lower cholesterol (such as red yeast rice, fish oil, omega 3 fatty acid) * Have undergone LDL apheresis in the past 1 year * Have recently used steroids, cyclosporine or isotretinoin * Have recently used an immunosuppressive therapy * Have recently received treatment with another antibody medication * Are currently using medications injected into the skin , except for single injections (for example flu vaccines) or injections into muscles * Are currently on a prescription or over-the-counter medicine for weight loss or are on a very low carbohydrate diet
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) | Baseline, Week 16 | Least square (LS) Means was calculated using analysis of covariance (ANCOVA) adjusted for disease classification, statin dose, baseline LDL-C measurement. Percent change from baseline response is the dependent variable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | Baseline, Week 16 | LS Mean was calculated using mixed model repeated measures (MMRM) analysis with baseline measurement, disease classification, statin dose, treatment, visit, and treatment by visit interaction included in the model. Percent change from baseline response is the dependent variable. |
| Percentage Change From Baseline in Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B) | Baseline, Week 16 | LS Mean was calculated using MMRM analysis with baseline measurement, disease classification, statin dose, treatment, visit, and treatment by visit interaction included in the model. Percent change from baseline response is the dependent variable. |
| Percentage Change From Baseline in Lipoprotein(a) [Lp(a)] | Baseline, Week 16 | Data was log-transformed for MMRM analysis, with change from baseline as the dependent variable, and baseline measurement, disease classification, statin dose, treatment, visit, and treatment by visit interaction included as independent variables. Percentage change from baseline in the original scale was then back-calculated from the log-transformed MMRM analysis. |
| Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) | Baseline, Week 16 | LS Mean was calculated using MMRM analysis with baseline measurement, disease classification, statin dose, treatment, visit, and treatment by visit interaction included in the model. Percent change from baseline response is the dependent variable. |
| Number of Participants Who Develop Treatment Emergent Anti-LY3015014 Antibodies | Baseline through Week 24 | — |
| Percentage Change From Baseline in Free Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels | Baseline, Week 16 | LS Mean was calculated using MMRM analysis with baseline measurement, disease classification, statin dose, treatment, visit, and treatment by visit interaction included in the model. Percent change from baseline response is the dependent variable. |
| Pharmacokinetics (PK): Area Under the Concentration-Time Curve at Steady-State (AUC,ss) for LY3015014 | Week 12-16 (Q4W) - Predose, Week 8-16 (Q8W) - Predose | — |
| Number of Participants With an Injection Site Reaction | Baseline through Week 24 | — |
| Percentage Change From Baseline in Total Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels | Baseline, Week 16 | LS Mean was calculated using MMRM analysis with baseline measurement, disease classification, statin dose, treatment, visit, and treatment by visit interaction included in the model. Percent change from baseline response is the dependent variable. |
Countries
Canada, Czechia, Denmark, Japan, Netherlands, Poland, Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Q4W Placebo given SC Q4W for 16 weeks.
Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe. | 87 |
| 20 mg LY3015014 Q4W 20 mg LY3015014 given subcutaneously SC Q4W for 16 weeks.
Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe. | 87 |
| 120 mg LY3015014 Q4W 120 mg LY3015014 given SC Q4W for 16 weeks.
Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe. | 86 |
| 300 mg LY3015014 Q4W 300 mg LY3015014 given SC Q4W for 16 weeks.
Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe. | 86 |
| 100 mg LY3015014 Q8W 100 mg LY3015014 given SC Q8W for 16 weeks.
Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe. | 86 |
| 300 mg LY3015014 Q8W 300 mg LY3015014 given SC Q8W for 16 weeks.
Participants will remain on stable diet and physician-prescribed statin therapy, if tolerated, with or without ezetimibe. | 87 |
| Total | 519 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 | 3 | 2 | 1 | 7 |
| Overall Study | Death | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 1 | 1 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 3 | 3 | 2 | 4 | 1 |
| Overall Study | Sponsor Decision | 2 | 0 | 1 | 3 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 3 | 4 | 2 | 3 | 3 | 1 |
Baseline characteristics
| Characteristic | 20 mg LY3015014 Q4W | 120 mg LY3015014 Q4W | Placebo Q4W | 300 mg LY3015014 Q4W | 100 mg LY3015014 Q8W | 300 mg LY3015014 Q8W | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 57.2 Years STANDARD_DEVIATION 9.4 | 57.1 Years STANDARD_DEVIATION 12.4 | 57.9 Years STANDARD_DEVIATION 11.2 | 59.7 Years STANDARD_DEVIATION 9.4 | 59.6 Years STANDARD_DEVIATION 8.1 | 58.7 Years STANDARD_DEVIATION 10.1 | 58.4 Years STANDARD_DEVIATION 10.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 1 Participants | 2 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 52 Participants | 56 Participants | 51 Participants | 51 Participants | 52 Participants | 315 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 32 Participants | 32 Participants | 28 Participants | 32 Participants | 34 Participants | 33 Participants | 191 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 22 Participants | 21 Participants | 25 Participants | 25 Participants | 21 Participants | 23 Participants | 137 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 6 Participants | 1 Participants | 1 Participants | 6 Participants | 5 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 61 Participants | 59 Participants | 60 Participants | 60 Participants | 58 Participants | 58 Participants | 356 Participants |
| Region of Enrollment Canada | 17 Participants | 13 Participants | 13 Participants | 15 Participants | 17 Participants | 19 Participants | 94 Participants |
| Region of Enrollment Czech Republic | 2 Participants | 3 Participants | 5 Participants | 4 Participants | 5 Participants | 4 Participants | 23 Participants |
| Region of Enrollment Denmark | 4 Participants | 5 Participants | 3 Participants | 6 Participants | 6 Participants | 5 Participants | 29 Participants |
| Region of Enrollment Japan | 18 Participants | 18 Participants | 17 Participants | 17 Participants | 18 Participants | 18 Participants | 106 Participants |
| Region of Enrollment Netherlands | 16 Participants | 17 Participants | 16 Participants | 11 Participants | 13 Participants | 15 Participants | 88 Participants |
| Region of Enrollment Poland | 7 Participants | 3 Participants | 6 Participants | 6 Participants | 5 Participants | 4 Participants | 31 Participants |
| Region of Enrollment Puerto Rico | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 5 Participants |
| Region of Enrollment United States | 23 Participants | 26 Participants | 25 Participants | 26 Participants | 22 Participants | 21 Participants | 143 Participants |
| Serum LDL Cholesterol Beta Quantification | 134.1 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 42.4 | 134.0 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 40.7 | 136.5 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 39.6 | 132.1 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 42.3 | 135.2 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 41.2 | 146.0 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 60.5 | 136.3 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 45 |
| Sex: Female, Male Female | 42 Participants | 41 Participants | 40 Participants | 39 Participants | 36 Participants | 43 Participants | 241 Participants |
| Sex: Female, Male Male | 45 Participants | 45 Participants | 47 Participants | 47 Participants | 50 Participants | 44 Participants | 278 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 63 / 87 | 69 / 87 | 64 / 86 | 64 / 86 | 64 / 86 | 58 / 87 |
| serious Total, serious adverse events | 5 / 87 | 3 / 87 | 6 / 86 | 2 / 86 | 2 / 86 | 4 / 87 |
Outcome results
Primary
Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C)
Least square (LS) Means was calculated using analysis of covariance (ANCOVA) adjusted for disease classification, statin dose, baseline LDL-C measurement. Percent change from baseline response is the dependent variable.
Time frame: Baseline, Week 16
Population: Modified Intent to Treat (mITT) is defined as all patients in the ITT population who had at least one baseline measurement and one post-randomization measurement of the variable that is analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q4W | Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) | 7.6 Percentage change | Standard Error 2.27 |
| 20 mg LY3015014 Q4W | Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) | -14.9 Percentage change | Standard Error 2.39 |
| 120 mg LY3015014 Q4W | Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) | -40.5 Percentage change | Standard Error 2.31 |
| 300 mg LY3015014 Q4W | Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) | -50.5 Percentage change | Standard Error 2.3 |
| 100 mg LY3015014 Q8W | Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) | -14.9 Percentage change | Standard Error 2.35 |
| 300 mg LY3015014 Q8W | Percentage Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) | -37.1 Percentage change | Standard Error 2.44 |
Secondary
Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP)
LS Mean was calculated using MMRM analysis with baseline measurement, disease classification, statin dose, treatment, visit, and treatment by visit interaction included in the model. Percent change from baseline response is the dependent variable.
Time frame: Baseline, Week 16
Population: mITT is defined as all patients in the ITT population who had at least one baseline measurement and one post-randomization measurement of the variable that is analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q4W | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) | 0.5 Percentage change | Standard Error 0.7 |
| 20 mg LY3015014 Q4W | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) | -0.2 Percentage change | Standard Error 0.72 |
| 120 mg LY3015014 Q4W | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) | 1.6 Percentage change | Standard Error 0.69 |
| 300 mg LY3015014 Q4W | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) | -0.3 Percentage change | Standard Error 0.7 |
| 100 mg LY3015014 Q8W | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) | -0.3 Percentage change | Standard Error 0.7 |
| 300 mg LY3015014 Q8W | Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) | -0.7 Percentage change | Standard Error 0.72 |
Secondary
Number of Participants Who Develop Treatment Emergent Anti-LY3015014 Antibodies
Time frame: Baseline through Week 24
Population: All randomized participants who received at least one dose of study treatment and had evaluable data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Q4W | Number of Participants Who Develop Treatment Emergent Anti-LY3015014 Antibodies | 4 Participants |
| 20 mg LY3015014 Q4W | Number of Participants Who Develop Treatment Emergent Anti-LY3015014 Antibodies | 6 Participants |
| 120 mg LY3015014 Q4W | Number of Participants Who Develop Treatment Emergent Anti-LY3015014 Antibodies | 10 Participants |
| 300 mg LY3015014 Q4W | Number of Participants Who Develop Treatment Emergent Anti-LY3015014 Antibodies | 5 Participants |
| 100 mg LY3015014 Q8W | Number of Participants Who Develop Treatment Emergent Anti-LY3015014 Antibodies | 4 Participants |
| 300 mg LY3015014 Q8W | Number of Participants Who Develop Treatment Emergent Anti-LY3015014 Antibodies | 3 Participants |
Secondary
Number of Participants With an Injection Site Reaction
Time frame: Baseline through Week 24
Population: All randomized participants who received at least one dose of study treatment and had evaluable data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Q4W | Number of Participants With an Injection Site Reaction | 26 Participants |
| 20 mg LY3015014 Q4W | Number of Participants With an Injection Site Reaction | 42 Participants |
| 120 mg LY3015014 Q4W | Number of Participants With an Injection Site Reaction | 57 Participants |
| 300 mg LY3015014 Q4W | Number of Participants With an Injection Site Reaction | 51 Participants |
| 100 mg LY3015014 Q8W | Number of Participants With an Injection Site Reaction | 36 Participants |
| 300 mg LY3015014 Q8W | Number of Participants With an Injection Site Reaction | 41 Participants |
Secondary
Percentage Change From Baseline in Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B)
LS Mean was calculated using MMRM analysis with baseline measurement, disease classification, statin dose, treatment, visit, and treatment by visit interaction included in the model. Percent change from baseline response is the dependent variable.
Time frame: Baseline, Week 16
Population: mITT is defined as all patients in the ITT population who had at least one baseline measurement and one post-randomization measurement of the variable that is analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Q4W | Percentage Change From Baseline in Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B) | Apo A1 | 0.3 Percentage change | Standard Error 1.4 |
| Placebo Q4W | Percentage Change From Baseline in Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B) | Apo B | 4.2 Percentage change | Standard Error 2.23 |
| 20 mg LY3015014 Q4W | Percentage Change From Baseline in Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B) | Apo A1 | 2.4 Percentage change | Standard Error 1.43 |
| 20 mg LY3015014 Q4W | Percentage Change From Baseline in Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B) | Apo B | -16.6 Percentage change | Standard Error 2.32 |
| 120 mg LY3015014 Q4W | Percentage Change From Baseline in Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B) | Apo A1 | 6.5 Percentage change | Standard Error 1.41 |
| 120 mg LY3015014 Q4W | Percentage Change From Baseline in Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B) | Apo B | -34.9 Percentage change | Standard Error 2.28 |
| 300 mg LY3015014 Q4W | Percentage Change From Baseline in Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B) | Apo A1 | 6.2 Percentage change | Standard Error 1.41 |
| 300 mg LY3015014 Q4W | Percentage Change From Baseline in Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B) | Apo B | -46.8 Percentage change | Standard Error 2.25 |
| 100 mg LY3015014 Q8W | Percentage Change From Baseline in Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B) | Apo A1 | 3.8 Percentage change | Standard Error 1.43 |
| 100 mg LY3015014 Q8W | Percentage Change From Baseline in Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B) | Apo B | -16.0 Percentage change | Standard Error 2.25 |
| 300 mg LY3015014 Q8W | Percentage Change From Baseline in Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B) | Apo A1 | 5.8 Percentage change | Standard Error 1.44 |
| 300 mg LY3015014 Q8W | Percentage Change From Baseline in Apolipoprotein A1 (Apo A1), Apolipoprotein B (Apo B) | Apo B | -31.9 Percentage change | Standard Error 2.31 |
Secondary
Percentage Change From Baseline in Free Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels
LS Mean was calculated using MMRM analysis with baseline measurement, disease classification, statin dose, treatment, visit, and treatment by visit interaction included in the model. Percent change from baseline response is the dependent variable.
Time frame: Baseline, Week 16
Population: mITT is defined as all patients in the ITT population who had at least one baseline measurement and one post-randomization measurement of the variable that is analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q4W | Percentage Change From Baseline in Free Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels | 9.9 Percentage change | Standard Error 5.59 |
| 20 mg LY3015014 Q4W | Percentage Change From Baseline in Free Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels | -16.3 Percentage change | Standard Error 5.81 |
| 120 mg LY3015014 Q4W | Percentage Change From Baseline in Free Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels | -36.6 Percentage change | Standard Error 5.67 |
| 300 mg LY3015014 Q4W | Percentage Change From Baseline in Free Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels | -68.0 Percentage change | Standard Error 5.71 |
| 100 mg LY3015014 Q8W | Percentage Change From Baseline in Free Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels | -4.4 Percentage change | Standard Error 5.8 |
| 300 mg LY3015014 Q8W | Percentage Change From Baseline in Free Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels | -35.2 Percentage change | Standard Error 5.72 |
Secondary
Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C
LS Mean was calculated using mixed model repeated measures (MMRM) analysis with baseline measurement, disease classification, statin dose, treatment, visit, and treatment by visit interaction included in the model. Percent change from baseline response is the dependent variable.
Time frame: Baseline, Week 16
Population: mITT is defined as all patients in the ITT population who had at least one baseline measurement and one post-randomization measurement of the variable that is analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | Non-HDL-C | 4.9 Percentage change | Standard Error 1.83 |
| Placebo Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | TG | 3.5 Percentage change | Standard Error 3.26 |
| Placebo Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | TC | 3.5 Percentage change | Standard Error 1.44 |
| Placebo Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | HDL-C | 1.6 Percentage change | Standard Error 1.58 |
| Placebo Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | LDL-C | 5.9 Percentage change | Standard Error 2.13 |
| 20 mg LY3015014 Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | TC | -10.5 Percentage change | Standard Error 1.47 |
| 20 mg LY3015014 Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | LDL-C | -18.0 Percentage change | Standard Error 2.18 |
| 20 mg LY3015014 Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | TG | -6.1 Percentage change | Standard Error 3.35 |
| 20 mg LY3015014 Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | HDL-C | 4.5 Percentage change | Standard Error 1.6 |
| 20 mg LY3015014 Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | Non-HDL-C | -16.1 Percentage change | Standard Error 1.86 |
| 120 mg LY3015014 Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | LDL-C | -46.4 Percentage change | Standard Error 2.15 |
| 120 mg LY3015014 Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | TG | -7.2 Percentage change | Standard Error 3.25 |
| 120 mg LY3015014 Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | TC | -27.8 Percentage change | Standard Error 1.44 |
| 120 mg LY3015014 Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | HDL-C | 7.3 Percentage change | Standard Error 1.57 |
| 120 mg LY3015014 Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | Non-HDL-C | -39.3 Percentage change | Standard Error 1.83 |
| 300 mg LY3015014 Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | LDL-C | -56.5 Percentage change | Standard Error 2.14 |
| 300 mg LY3015014 Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | HDL-C | 8.8 Percentage change | Standard Error 1.58 |
| 300 mg LY3015014 Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | TC | -34.1 Percentage change | Standard Error 1.44 |
| 300 mg LY3015014 Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | TG | -15.1 Percentage change | Standard Error 3.26 |
| 300 mg LY3015014 Q4W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | Non-HDL-C | -48.9 Percentage change | Standard Error 1.83 |
| 100 mg LY3015014 Q8W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | TG | -7.2 Percentage change | Standard Error 3.29 |
| 100 mg LY3015014 Q8W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | TC | -11.0 Percentage change | Standard Error 1.45 |
| 100 mg LY3015014 Q8W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | Non-HDL-C | -16.1 Percentage change | Standard Error 1.84 |
| 100 mg LY3015014 Q8W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | LDL-C | -18.4 Percentage change | Standard Error 2.14 |
| 100 mg LY3015014 Q8W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | HDL-C | 4.5 Percentage change | Standard Error 1.59 |
| 300 mg LY3015014 Q8W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | Non-HDL-C | -35.8 Percentage change | Standard Error 1.88 |
| 300 mg LY3015014 Q8W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | TG | -10.6 Percentage change | Standard Error 3.35 |
| 300 mg LY3015014 Q8W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | LDL-C | -42.2 Percentage change | Standard Error 2.21 |
| 300 mg LY3015014 Q8W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | HDL-C | 8.4 Percentage change | Standard Error 1.61 |
| 300 mg LY3015014 Q8W | Percentage Change From Baseline in LDL-C, Total Cholesterol (TC), High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides (TG), Non-HDL-C | TC | -24.6 Percentage change | Standard Error 1.48 |
Secondary
Percentage Change From Baseline in Lipoprotein(a) [Lp(a)]
Data was log-transformed for MMRM analysis, with change from baseline as the dependent variable, and baseline measurement, disease classification, statin dose, treatment, visit, and treatment by visit interaction included as independent variables. Percentage change from baseline in the original scale was then back-calculated from the log-transformed MMRM analysis.
Time frame: Baseline, Week 16
Population: mITT is defined as all patients in the ITT population who had at least one baseline measurement and one post-randomization measurement of the variable that is analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q4W | Percentage Change From Baseline in Lipoprotein(a) [Lp(a)] | -0.31 Percentage Change | Standard Error 0.0436 |
| 20 mg LY3015014 Q4W | Percentage Change From Baseline in Lipoprotein(a) [Lp(a)] | -16.63 Percentage Change | Standard Error 0.0442 |
| 120 mg LY3015014 Q4W | Percentage Change From Baseline in Lipoprotein(a) [Lp(a)] | -19.02 Percentage Change | Standard Error 0.0427 |
| 300 mg LY3015014 Q4W | Percentage Change From Baseline in Lipoprotein(a) [Lp(a)] | -37.29 Percentage Change | Standard Error 0.042 |
| 100 mg LY3015014 Q8W | Percentage Change From Baseline in Lipoprotein(a) [Lp(a)] | -7.54 Percentage Change | Standard Error 0.0427 |
| 300 mg LY3015014 Q8W | Percentage Change From Baseline in Lipoprotein(a) [Lp(a)] | -21.01 Percentage Change | Standard Error 0.0437 |
Secondary
Percentage Change From Baseline in Total Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels
LS Mean was calculated using MMRM analysis with baseline measurement, disease classification, statin dose, treatment, visit, and treatment by visit interaction included in the model. Percent change from baseline response is the dependent variable.
Time frame: Baseline, Week 16
Population: mITT is defined as all patients in the ITT population who had at least one baseline measurement and one post-randomization measurement of the variable that is analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q4W | Percentage Change From Baseline in Total Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels | 14.6 Percentage change | Standard Error 13.66 |
| 20 mg LY3015014 Q4W | Percentage Change From Baseline in Total Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels | 9.1 Percentage change | Standard Error 14 |
| 120 mg LY3015014 Q4W | Percentage Change From Baseline in Total Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels | 86.4 Percentage change | Standard Error 13.65 |
| 300 mg LY3015014 Q4W | Percentage Change From Baseline in Total Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels | 130.6 Percentage change | Standard Error 13.63 |
| 100 mg LY3015014 Q8W | Percentage Change From Baseline in Total Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels | 21.8 Percentage change | Standard Error 13.63 |
| 300 mg LY3015014 Q8W | Percentage Change From Baseline in Total Proprotein Convertase Subtilisin/Kexin Type 9 Antibody (PCSK9) Levels | 41.0 Percentage change | Standard Error 13.63 |
Secondary
Pharmacokinetics (PK): Area Under the Concentration-Time Curve at Steady-State (AUC,ss) for LY3015014
Time frame: Week 12-16 (Q4W) - Predose, Week 8-16 (Q8W) - Predose
Population: All randomly assigned participants who received at least one dose of the study medication and had evaluable data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q4W | Pharmacokinetics (PK): Area Under the Concentration-Time Curve at Steady-State (AUC,ss) for LY3015014 | 1590 μg∙hr/mL | Geometric Coefficient of Variation 29.2 |
| 20 mg LY3015014 Q4W | Pharmacokinetics (PK): Area Under the Concentration-Time Curve at Steady-State (AUC,ss) for LY3015014 | 9670 μg∙hr/mL | Geometric Coefficient of Variation 29.9 |
| 120 mg LY3015014 Q4W | Pharmacokinetics (PK): Area Under the Concentration-Time Curve at Steady-State (AUC,ss) for LY3015014 | 27300 μg∙hr/mL | Geometric Coefficient of Variation 26.3 |
| 300 mg LY3015014 Q4W | Pharmacokinetics (PK): Area Under the Concentration-Time Curve at Steady-State (AUC,ss) for LY3015014 | 7800 μg∙hr/mL | Geometric Coefficient of Variation 28.5 |
| 100 mg LY3015014 Q8W | Pharmacokinetics (PK): Area Under the Concentration-Time Curve at Steady-State (AUC,ss) for LY3015014 | 26600 μg∙hr/mL | Geometric Coefficient of Variation 32.2 |