Hyperlipidemia or Mixed Dyslipidemia at High Risk for Cardiovascular Events
Conditions
Keywords
Japanese, high cholesterol, LDL-C, High Cardiovascular Risk
Brief summary
The primary objective of the study was to evaluate the effect of 12 weeks of subcutaneous evolocumab administered every 2 weeks and once a month, compared with placebo, on percent change from baseline in LDL-C when used in combination with statin therapy in adults with high cardiovascular risk and with hyperlipidemia or mixed dyslipidemia.
Detailed description
After a screening and placebo run-in period, eligible patients were randomized in a 1:1 ratio to 1 of 2 open-label background statin treatments (atorvastatin 5 mg or 20 mg daily \[QD\]) and entered a 4-week lipid stabilization period. After the lipid stabilization period, eligible patients were randomized in a 1:1:1:1 ratio to investigational product (evolocumab or placebo) for the 12-week treatment period. Both randomizations were stratified by subject diagnosis and lipid-lowering therapy as follows: * current or prior diagnosis of heterozygous familial hypercholesterolemia (HeFH) * no diagnosis of HeFH and receiving intensive lipid-lowering therapy * no diagnosis of HeFH and receiving non-intensive lipid-lowering therapy. A participant was considered randomized into the study after successfully completing the screening period, meeting all inclusion/exclusion criteria including meeting final laboratory safety criteria, and undergoing both randomization procedures.
Interventions
DRUGAtorvastatin
Administered orally once a day
BIOLOGICALEvolocumab
Administered by subcutaneous injection
Administered by subcutaneous injection
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Male or female, Japanese adult, 20-85 years of age; Subjects on stable dose of statin for greater than equal to 4 weeks; Fasting LDL-C greater than equal to 100 mg/dL; Fasting triglycerides less than equal to 400 mg/dL; Subject is at high risk for cardiovascular events.
Exclusion criteria
New York heart Association (NYHA) III or IV - heart failure; Uncontrolled cardiac arrhythmia; Uncontrolled hypertension; Type 1 diabetes, poorly controlled type 2 diabetes; Uncontrolled hypothyroidism or hyperthyroidism
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | Baseline and Week 12 |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in Total Cholesterol at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in the Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12 | Baseline and Week 12 |
| Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL | Weeks 10 and 12 |
| Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 | Week 12 |
| Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in Apolipoprotein B at Week 12 | Baseline and Week 12 |
| Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Change From Baseline in LDL-C at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in Non-HDL-C at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in Lipoprotein(a) at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in Triglycerides at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in HDL-C at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in VLDL-C at Week 12 | Baseline and Week 12 |
Countries
Japan
Participant flow
Recruitment details
Japanese men and women ≥ 20 to ≤ 85 years of age, with fasting low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (2.6 mmol/L), fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L), and at high risk for cardiovascular events were eligible to participate. First patient enrolled on 07 October 2013 and last patient enrolled on 17 February 2014.
Pre-assignment details
409 participants were randomized to 1 of 2 open-label atorvastatin cohorts (5 mg or 20 mg) for the lipid stabilization period; 404 were then randomized to blinded investigational product. Both randomizations were stratified by heterozygous familial hypercholesterolemia (HeFH) diagnosis and lipid-lowering therapy.
Participants by arm
| Arm | Count |
|---|---|
| A5 Placebo Q2W Participants received atorvastatin 5 mg (A5) daily during the 4 week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks. | 49 |
| A5 Placebo QM Participants received atorvastatin 5 mg daily during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month (QM) for 12 weeks. | 50 |
| A5 Evolocumab Q2W Participants received atorvastatin 5 mg daily during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. | 50 |
| A5 Evolocumab QM Participants received atorvastatin 5 mg daily during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for 12 weeks. | 50 |
| A20 Placebo Q2W Participants received atorvastatin 20 mg (A20) daily during the 4 week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for 12 weeks. | 52 |
| A20 Placebo QM Participants received atorvastatin 20 mg daily during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for 12 weeks. | 51 |
| A20 Evolocumab Q2W Participants received atorvastatin 20 mg daily during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. | 51 |
| A20 Evolocumab QM Participants received atorvastatin 20 mg daily during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for 12 weeks. | 51 |
| Total | 404 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | A5 Placebo Q2W | Total | A20 Evolocumab QM | A20 Evolocumab Q2W | A20 Placebo QM | A20 Placebo Q2W | A5 Evolocumab QM | A5 Evolocumab Q2W | A5 Placebo QM |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 62.1 years STANDARD_DEVIATION 9.9 | 61.3 years STANDARD_DEVIATION 10.3 | 61.8 years STANDARD_DEVIATION 11.9 | 60.1 years STANDARD_DEVIATION 9.9 | 60.4 years STANDARD_DEVIATION 10.5 | 60.4 years STANDARD_DEVIATION 10.4 | 60.1 years STANDARD_DEVIATION 11.6 | 65.2 years STANDARD_DEVIATION 7.8 | 60.6 years STANDARD_DEVIATION 9.9 |
| Apolipoprotein B/Apolipoprotein A-1 Ratio | 0.633 ratio STANDARD_DEVIATION 0.16 | 0.595 ratio STANDARD_DEVIATION 0.179 | 0.576 ratio STANDARD_DEVIATION 0.176 | 0.575 ratio STANDARD_DEVIATION 0.177 | 0.524 ratio STANDARD_DEVIATION 0.108 | 0.529 ratio STANDARD_DEVIATION 0.118 | 0.658 ratio STANDARD_DEVIATION 0.235 | 0.643 ratio STANDARD_DEVIATION 0.223 | 0.628 ratio STANDARD_DEVIATION 0.152 |
| Apolipoprotein B Concentration | 99.0 mg/dL STANDARD_DEVIATION 20 | 93.7 mg/dL STANDARD_DEVIATION 22.8 | 87.7 mg/dL STANDARD_DEVIATION 19.6 | 87.2 mg/dL STANDARD_DEVIATION 19.1 | 82.7 mg/dL STANDARD_DEVIATION 14.6 | 85.7 mg/dL STANDARD_DEVIATION 18.4 | 102.2 mg/dL STANDARD_DEVIATION 24.7 | 105.1 mg/dL STANDARD_DEVIATION 31.2 | 100.6 mg/dL STANDARD_DEVIATION 20 |
| HDL-C Concentration | 57.5 mg/dL STANDARD_DEVIATION 13.6 | 57.1 mg/dL STANDARD_DEVIATION 14 | 56.3 mg/dL STANDARD_DEVIATION 15.7 | 55.9 mg/dL STANDARD_DEVIATION 14.4 | 56.0 mg/dL STANDARD_DEVIATION 11.3 | 59.6 mg/dL STANDARD_DEVIATION 15.4 | 54.7 mg/dL STANDARD_DEVIATION 13.9 | 58.6 mg/dL STANDARD_DEVIATION 12.7 | 58.3 mg/dL STANDARD_DEVIATION 14.6 |
| LDL-C Concentration | 115.7 mg/dL STANDARD_DEVIATION 26 | 105.5 mg/dL STANDARD_DEVIATION 32 | 98.0 mg/dL STANDARD_DEVIATION 25.6 | 95.8 mg/dL STANDARD_DEVIATION 23.6 | 90.7 mg/dL STANDARD_DEVIATION 20.8 | 90.9 mg/dL STANDARD_DEVIATION 25.5 | 118.8 mg/dL STANDARD_DEVIATION 36.6 | 121.9 mg/dL STANDARD_DEVIATION 44.6 | 114.0 mg/dL STANDARD_DEVIATION 29.2 |
| Lipoprotein(a) Concentration | 35.0 nmol/L | 33.0 nmol/L | 28.0 nmol/L | 33.0 nmol/L | 35.0 nmol/L | 30.0 nmol/L | 36.5 nmol/L | 36.0 nmol/L | 29.5 nmol/L |
| Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration | 142.0 mg/dL STANDARD_DEVIATION 30.4 | 132.7 mg/dL STANDARD_DEVIATION 35.9 | 122.7 mg/dL STANDARD_DEVIATION 29.5 | 121.8 mg/dL STANDARD_DEVIATION 29.8 | 117.5 mg/dL STANDARD_DEVIATION 25.1 | 118.2 mg/dL STANDARD_DEVIATION 28.6 | 147.8 mg/dL STANDARD_DEVIATION 39.6 | 151.8 mg/dL STANDARD_DEVIATION 48.8 | 141.2 mg/dL STANDARD_DEVIATION 31.8 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 49 participants | 404 participants | 51 participants | 51 participants | 51 participants | 52 participants | 50 participants | 50 participants | 50 participants |
| Race/Ethnicity, Customized Black or African American | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized White | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 22 Participants | 160 Participants | 24 Participants | 16 Participants | 18 Participants | 24 Participants | 18 Participants | 23 Participants | 15 Participants |
| Sex: Female, Male Male | 27 Participants | 244 Participants | 27 Participants | 35 Participants | 33 Participants | 28 Participants | 32 Participants | 27 Participants | 35 Participants |
| Stratification Factor Diagnosis of HeFH | 3 participants | 21 participants | 3 participants | 3 participants | 2 participants | 3 participants | 3 participants | 2 participants | 2 participants |
| Stratification Factor Non-HeFH and Intensive Statin Use | 10 participants | 85 participants | 11 participants | 11 participants | 11 participants | 11 participants | 10 participants | 11 participants | 10 participants |
| Stratification Factor Non-HeFH and Non-Intensive Statin Use | 36 participants | 298 participants | 37 participants | 37 participants | 38 participants | 38 participants | 37 participants | 37 participants | 38 participants |
| Total Cholesterol Concentration | 199.5 mg/dL STANDARD_DEVIATION 30.7 | 189.8 mg/dL STANDARD_DEVIATION 36.3 | 179.0 mg/dL STANDARD_DEVIATION 29.4 | 177.7 mg/dL STANDARD_DEVIATION 26.2 | 173.6 mg/dL STANDARD_DEVIATION 29.2 | 177.8 mg/dL STANDARD_DEVIATION 33 | 202.5 mg/dL STANDARD_DEVIATION 38.4 | 210.4 mg/dL STANDARD_DEVIATION 47.9 | 199.4 mg/dL STANDARD_DEVIATION 33.2 |
| Total Cholesterol/HDL-C Ratio | 3.618 ratio STANDARD_DEVIATION 0.891 | 3.491 ratio STANDARD_DEVIATION 1.018 | 3.400 ratio STANDARD_DEVIATION 1.071 | 3.392 ratio STANDARD_DEVIATION 1.112 | 3.170 ratio STANDARD_DEVIATION 0.612 | 3.116 ratio STANDARD_DEVIATION 0.76 | 3.933 ratio STANDARD_DEVIATION 1.295 | 3.743 ratio STANDARD_DEVIATION 1.186 | 3.579 ratio STANDARD_DEVIATION 0.827 |
| Triglyceride Concentration | 125.0 mg/dL | 121.5 mg/dL | 113.0 mg/dL | 109.0 mg/dL | 120.0 mg/dL | 120.0 mg/dL | 132.0 mg/dL | 125.0 mg/dL | 128.5 mg/dL |
| Very-Low-Density Lipoprotein Cholesterol (VLDL-C) Concentration | 26.3 mg/dL STANDARD_DEVIATION 11 | 26.6 mg/dL STANDARD_DEVIATION 11.5 | 24.7 mg/dL STANDARD_DEVIATION 10.3 | 24.3 mg/dL STANDARD_DEVIATION 10.7 | 25.1 mg/dL STANDARD_DEVIATION 9.4 | 27.4 mg/dL STANDARD_DEVIATION 12 | 29.0 mg/dL STANDARD_DEVIATION 12.8 | 29.2 mg/dL STANDARD_DEVIATION 14.7 | 26.8 mg/dL STANDARD_DEVIATION 10.2 |
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 | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 49 | 11 / 50 | 13 / 50 | 9 / 50 | 6 / 52 | 14 / 51 | 7 / 51 | 12 / 51 |
| serious Total, serious adverse events | 1 / 49 | 2 / 50 | 0 / 50 | 1 / 50 | 1 / 52 | 1 / 51 | 0 / 51 | 0 / 51 |
Outcome results
Primary
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12 | 0.27 percent change | Standard Error 2.21 |
| A5 Placebo QM | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12 | 3.91 percent change | Standard Error 2.09 |
| A5 Evolocumab Q2W | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12 | -73.70 percent change | Standard Error 2.26 |
| A5 Evolocumab QM | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12 | -69.98 percent change | Standard Error 2.02 |
| A20 Placebo Q2W | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12 | -0.42 percent change | Standard Error 3.26 |
| A20 Placebo QM | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12 | -2.67 percent change | Standard Error 2.31 |
| A20 Evolocumab Q2W | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12 | -74.82 percent change | Standard Error 3.26 |
| A20 Evolocumab QM | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12 | -76.93 percent change | Standard Error 2.24 |
Comparison: The null hypothesis was that there was no difference in the percent change from baseline at the mean of Weeks 10 and 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.p-value: <0.00195% CI: [-78.54, -69.41]Repeated measures linear effects model
Comparison: The null hypothesis was that there was no difference in the percent change from baseline at the mean of Weeks 10 and 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.p-value: <0.00195% CI: [-77.22, -68.57]Repeated measures linear effects model
Comparison: The null hypothesis was that there was no difference in the percent change from baseline at the mean of Weeks 10 and 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.p-value: <0.00195% CI: [-81.21, -67.61]Repeated measures linear effects model
Comparison: The null hypothesis was that there was no difference in the percent change from baseline at the mean of Weeks 10 and 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.p-value: <0.00195% CI: [-78.93, -69.6]Repeated measures linear effects model
Primary
Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | 1.28 percent change | Standard Error 2.43 |
| A5 Placebo QM | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | 5.29 percent change | Standard Error 2.19 |
| A5 Evolocumab Q2W | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -73.57 percent change | Standard Error 2.48 |
| A5 Evolocumab QM | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -64.62 percent change | Standard Error 2.12 |
| A20 Placebo Q2W | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | 1.39 percent change | Standard Error 3.51 |
| A20 Placebo QM | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -3.49 percent change | Standard Error 2.67 |
| A20 Evolocumab Q2W | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -74.46 percent change | Standard Error 3.5 |
| A20 Evolocumab QM | Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -70.36 percent change | Standard Error 2.61 |
Comparison: The null hypothesis was that there was no difference in the percent change from baseline at Week 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.p-value: <0.00195% CI: [-80.22, -69.47]Repeated measures linear effects model
Comparison: The null hypothesis was that there was no difference in the percent change from baseline at Week 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.p-value: <0.00195% CI: [-74.6, -65.23]Repeated measures linear effects model
Comparison: The null hypothesis was that there was no difference in the percent change from baseline at Week 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.p-value: <0.00195% CI: [-83.55, -68.15]Repeated measures linear effects model
Comparison: The null hypothesis was that there was no difference in the percent change from baseline at Week 12 in LDL-C between evolocumab and placebo, and the alternative hypothesis was that a mean difference did exist.p-value: <0.00195% CI: [-72.88, -60.87]Repeated measures linear effects model
Secondary
Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -14.8 mg/dL | Standard Error 4.3 |
| A5 Placebo QM | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -2.6 mg/dL | Standard Error 4.3 |
| A5 Evolocumab Q2W | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -104.1 mg/dL | Standard Error 4.4 |
| A5 Evolocumab QM | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -88.9 mg/dL | Standard Error 4.1 |
| A20 Placebo Q2W | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -8.9 mg/dL | Standard Error 3.2 |
| A20 Placebo QM | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -5.7 mg/dL | Standard Error 3.7 |
| A20 Evolocumab Q2W | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -77.6 mg/dL | Standard Error 3.2 |
| A20 Evolocumab QM | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -77.7 mg/dL | Standard Error 3.6 |
p-value: <0.00195% CI: [-98.4, -80.2]Repeated measures linear effects model
p-value: <0.00195% CI: [-95.1, -77.5]Repeated measures linear effects model
p-value: <0.00195% CI: [-75.3, -62.1]Repeated measures linear effects model
p-value: <0.00195% CI: [-79.5, -64.6]Repeated measures linear effects model
Secondary
Change From Baseline in LDL-C at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Change From Baseline in LDL-C at Week 12 | -13.7 mg/dL | Standard Error 4.6 |
| A5 Placebo QM | Change From Baseline in LDL-C at Week 12 | -0.4 mg/dL | Standard Error 4.3 |
| A5 Evolocumab Q2W | Change From Baseline in LDL-C at Week 12 | -104.5 mg/dL | Standard Error 4.6 |
| A5 Evolocumab QM | Change From Baseline in LDL-C at Week 12 | -84.0 mg/dL | Standard Error 4.2 |
| A20 Placebo Q2W | Change From Baseline in LDL-C at Week 12 | -7.7 mg/dL | Standard Error 3.3 |
| A20 Placebo QM | Change From Baseline in LDL-C at Week 12 | -6.2 mg/dL | Standard Error 4 |
| A20 Evolocumab Q2W | Change From Baseline in LDL-C at Week 12 | -77.2 mg/dL | Standard Error 3.3 |
| A20 Evolocumab QM | Change From Baseline in LDL-C at Week 12 | -71.7 mg/dL | Standard Error 3.9 |
p-value: <0.00195% CI: [-100.9, -80.7]Repeated measures linear effects model
p-value: <0.00195% CI: [-92.5, -74.8]Repeated measures linear effects model
p-value: <0.00195% CI: [-76.5, -62.6]Repeated measures linear effects model
p-value: <0.00195% CI: [-73.8, -57.1]Repeated measures linear effects model
Secondary
Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL
Time frame: Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL | 0.0 percentage of participants | 95% Confidence Interval 2.02 |
| A5 Placebo QM | Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL | 0.0 percentage of participants | 95% Confidence Interval 2.37 |
| A5 Evolocumab Q2W | Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL | 98.0 percentage of participants | 95% Confidence Interval 2.07 |
| A5 Evolocumab QM | Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL | 96.0 percentage of participants | 95% Confidence Interval 2.29 |
| A20 Placebo Q2W | Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL | 22.4 percentage of participants | 95% Confidence Interval 2.3 |
| A20 Placebo QM | Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL | 15.7 percentage of participants | 95% Confidence Interval 2.09 |
| A20 Evolocumab Q2W | Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL | 96.0 percentage of participants | 95% Confidence Interval 2.3 |
| A20 Evolocumab QM | Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL | 98.0 percentage of participants | 95% Confidence Interval 2.02 |
p-value: <0.00195% CI: [86.8, 99.6]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [84.1, 98.9]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [57.1, 83.4]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [67.5, 90]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12
Time frame: Week 12
Population: Full analysis set
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 | 0.0 percentage of participants | 95% Confidence Interval 2.02 |
| A5 Placebo QM | Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 | 4.2 percentage of participants | 95% Confidence Interval 2.37 |
| A5 Evolocumab Q2W | Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 | 98.0 percentage of participants | 95% Confidence Interval 2.07 |
| A5 Evolocumab QM | Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 | 96.0 percentage of participants | 95% Confidence Interval 2.29 |
| A20 Placebo Q2W | Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 | 20.4 percentage of participants | 95% Confidence Interval 2.3 |
| A20 Placebo QM | Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 | 20.0 percentage of participants | 95% Confidence Interval 2.09 |
| A20 Evolocumab Q2W | Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 | 96.0 percentage of participants | 95% Confidence Interval 2.3 |
| A20 Evolocumab QM | Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 | 98.0 percentage of participants | 95% Confidence Interval 2.02 |
p-value: <0.00195% CI: [86.7, 99.6]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [78.2, 96]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [59.3, 85]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [62.6, 86.9]Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at the Mean of Weeks 10 and 12 | 0.06 percent change | Standard Error 2.02 |
| A5 Placebo QM | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at the Mean of Weeks 10 and 12 | 2.79 percent change | Standard Error 2.37 |
| A5 Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at the Mean of Weeks 10 and 12 | -66.41 percent change | Standard Error 2.07 |
| A5 Evolocumab QM | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at the Mean of Weeks 10 and 12 | -61.55 percent change | Standard Error 2.29 |
| A20 Placebo Q2W | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at the Mean of Weeks 10 and 12 | -1.92 percent change | Standard Error 2.3 |
| A20 Placebo QM | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at the Mean of Weeks 10 and 12 | 1.54 percent change | Standard Error 2.09 |
| A20 Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at the Mean of Weeks 10 and 12 | -65.97 percent change | Standard Error 2.3 |
| A20 Evolocumab QM | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at the Mean of Weeks 10 and 12 | -65.72 percent change | Standard Error 2.02 |
p-value: <0.00195% CI: [-70.58, -62.36]Repeated measures linear effects model
p-value: <0.00195% CI: [-69.01, -59.66]Repeated measures linear effects model
p-value: <0.00195% CI: [-68.9, -59.2]Repeated measures linear effects model
p-value: <0.00195% CI: [-71.36, -63.15]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | -0.32 percent change | Standard Error 1.98 |
| A5 Placebo QM | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | 0.76 percent change | Standard Error 2.06 |
| A5 Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | -64.76 percent change | Standard Error 2.03 |
| A5 Evolocumab QM | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | -58.47 percent change | Standard Error 1.99 |
| A20 Placebo Q2W | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | -4.32 percent change | Standard Error 2.27 |
| A20 Placebo QM | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | -0.85 percent change | Standard Error 1.9 |
| A20 Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | -64.38 percent change | Standard Error 2.27 |
| A20 Evolocumab QM | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | -64.24 percent change | Standard Error 1.84 |
p-value: <0.00195% CI: [-68.49, -60.39]Repeated measures linear effects model
p-value: <0.00195% CI: [-63.3, -55.17]Repeated measures linear effects model
p-value: <0.00195% CI: [-64.87, -55.25]Repeated measures linear effects model
p-value: <0.00195% CI: [-67.15, -59.62]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Apolipoprotein B at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in Apolipoprotein B at Week 12 | 0.74 percent change | Standard Error 2.17 |
| A5 Placebo QM | Percent Change From Baseline in Apolipoprotein B at Week 12 | 2.42 percent change | Standard Error 2.26 |
| A5 Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B at Week 12 | -64.83 percent change | Standard Error 2.22 |
| A5 Evolocumab QM | Percent Change From Baseline in Apolipoprotein B at Week 12 | -54.80 percent change | Standard Error 2.19 |
| A20 Placebo Q2W | Percent Change From Baseline in Apolipoprotein B at Week 12 | -2.47 percent change | Standard Error 2.48 |
| A20 Placebo QM | Percent Change From Baseline in Apolipoprotein B at Week 12 | -1.89 percent change | Standard Error 2.17 |
| A20 Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B at Week 12 | -62.83 percent change | Standard Error 2.47 |
| A20 Evolocumab QM | Percent Change From Baseline in Apolipoprotein B at Week 12 | -58.04 percent change | Standard Error 2.11 |
p-value: <0.00195% CI: [-70.34, -60.79]Repeated measures linear effects model
p-value: <0.00195% CI: [-62.05, -52.4]Repeated measures linear effects model
p-value: <0.00195% CI: [-65.91, -54.83]Repeated measures linear effects model
p-value: <0.00195% CI: [-60.92, -51.39]Repeated measures linear effects model
Secondary
Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 | -4.83 percent change | Standard Error 2.25 |
| A5 Placebo QM | Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 | -1.57 percent change | Standard Error 2.29 |
| A5 Evolocumab Q2W | Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 | 7.50 percent change | Standard Error 2.3 |
| A5 Evolocumab QM | Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 | 13.05 percent change | Standard Error 2.22 |
| A20 Placebo Q2W | Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 | -4.03 percent change | Standard Error 2.34 |
| A20 Placebo QM | Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 | -3.06 percent change | Standard Error 2.13 |
| A20 Evolocumab Q2W | Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 | 11.34 percent change | Standard Error 2.33 |
| A20 Evolocumab QM | Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 | 6.09 percent change | Standard Error 2.07 |
p-value: <0.00195% CI: [7.39, 17.27]Repeated measures linear effects model
p-value: <0.00195% CI: [9.93, 19.3]Repeated measures linear effects model
p-value: <0.00195% CI: [10.12, 20.6]Repeated measures linear effects model
p-value: 0.00195% CI: [4.67, 13.62]Repeated measures linear effects model
Secondary
Percent Change From Baseline in HDL-C at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in HDL-C at Week 12 | -4.59 percent change | Standard Error 2.58 |
| A5 Placebo QM | Percent Change From Baseline in HDL-C at Week 12 | -0.40 percent change | Standard Error 2.47 |
| A5 Evolocumab Q2W | Percent Change From Baseline in HDL-C at Week 12 | 8.88 percent change | Standard Error 2.62 |
| A5 Evolocumab QM | Percent Change From Baseline in HDL-C at Week 12 | 14.80 percent change | Standard Error 2.39 |
| A20 Placebo Q2W | Percent Change From Baseline in HDL-C at Week 12 | -3.57 percent change | Standard Error 2.59 |
| A20 Placebo QM | Percent Change From Baseline in HDL-C at Week 12 | -2.36 percent change | Standard Error 2.38 |
| A20 Evolocumab Q2W | Percent Change From Baseline in HDL-C at Week 12 | 13.28 percent change | Standard Error 2.58 |
| A20 Evolocumab QM | Percent Change From Baseline in HDL-C at Week 12 | 7.84 percent change | Standard Error 2.32 |
p-value: <0.00195% CI: [7.4, 19.53]Repeated measures linear effects model
p-value: <0.00195% CI: [9.87, 20.52]Repeated measures linear effects model
p-value: <0.00195% CI: [10.74, 22.95]Repeated measures linear effects model
p-value: 0.00195% CI: [4.85, 15.55]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12 | 5.23 percent change | Standard Error 6.18 |
| A5 Placebo QM | Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12 | 4.07 percent change | Standard Error 4.95 |
| A5 Evolocumab Q2W | Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12 | -45.97 percent change | Standard Error 6.27 |
| A5 Evolocumab QM | Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12 | -45.01 percent change | Standard Error 4.78 |
| A20 Placebo Q2W | Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12 | 6.52 percent change | Standard Error 4.81 |
| A20 Placebo QM | Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12 | -5.62 percent change | Standard Error 5 |
| A20 Evolocumab Q2W | Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12 | -43.03 percent change | Standard Error 4.81 |
| A20 Evolocumab QM | Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12 | -49.55 percent change | Standard Error 4.85 |
p-value: <0.00195% CI: [-63.88, -38.52]Repeated measures linear effects model
p-value: <0.00195% CI: [-58.89, -39.27]Repeated measures linear effects model
p-value: <0.00195% CI: [-59.74, -39.35]Repeated measures linear effects model
p-value: <0.00195% CI: [-53.75, -34.12]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Lipoprotein(a) at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in Lipoprotein(a) at Week 12 | 4.35 percent change | Standard Error 6.86 |
| A5 Placebo QM | Percent Change From Baseline in Lipoprotein(a) at Week 12 | 7.03 percent change | Standard Error 5.47 |
| A5 Evolocumab Q2W | Percent Change From Baseline in Lipoprotein(a) at Week 12 | -45.72 percent change | Standard Error 6.93 |
| A5 Evolocumab QM | Percent Change From Baseline in Lipoprotein(a) at Week 12 | -41.74 percent change | Standard Error 5.29 |
| A20 Placebo Q2W | Percent Change From Baseline in Lipoprotein(a) at Week 12 | 10.75 percent change | Standard Error 5.15 |
| A20 Placebo QM | Percent Change From Baseline in Lipoprotein(a) at Week 12 | -5.73 percent change | Standard Error 5.18 |
| A20 Evolocumab Q2W | Percent Change From Baseline in Lipoprotein(a) at Week 12 | -41.93 percent change | Standard Error 5.13 |
| A20 Evolocumab QM | Percent Change From Baseline in Lipoprotein(a) at Week 12 | -45.70 percent change | Standard Error 5.02 |
p-value: <0.00195% CI: [-65.25, -34.9]Repeated measures linear effects model
p-value: <0.00195% CI: [-60.49, -37.05]Repeated measures linear effects model
p-value: <0.00195% CI: [-64.06, -41.3]Repeated measures linear effects model
p-value: <0.00195% CI: [-50.46, -29.48]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | 0.18 percent change | Standard Error 2.13 |
| A5 Placebo QM | Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | 4.26 percent change | Standard Error 1.86 |
| A5 Evolocumab Q2W | Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | -68.48 percent change | Standard Error 2.18 |
| A5 Evolocumab QM | Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | -61.69 percent change | Standard Error 1.8 |
| A20 Placebo Q2W | Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | -1.57 percent change | Standard Error 2.45 |
| A20 Placebo QM | Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | -1.79 percent change | Standard Error 1.94 |
| A20 Evolocumab Q2W | Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | -69.72 percent change | Standard Error 2.45 |
| A20 Evolocumab QM | Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | -69.07 percent change | Standard Error 1.88 |
p-value: <0.00195% CI: [-73.06, -64.27]Repeated measures linear effects model
p-value: <0.00195% CI: [-69.74, -62.16]Repeated measures linear effects model
p-value: <0.00195% CI: [-73.3, -62.99]Repeated measures linear effects model
p-value: <0.00195% CI: [-71.14, -63.42]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Non-HDL-C at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in Non-HDL-C at Week 12 | 1.12 percent change | Standard Error 2.3 |
| A5 Placebo QM | Percent Change From Baseline in Non-HDL-C at Week 12 | 5.55 percent change | Standard Error 2.02 |
| A5 Evolocumab Q2W | Percent Change From Baseline in Non-HDL-C at Week 12 | -67.81 percent change | Standard Error 2.35 |
| A5 Evolocumab QM | Percent Change From Baseline in Non-HDL-C at Week 12 | -58.03 percent change | Standard Error 1.96 |
| A20 Placebo Q2W | Percent Change From Baseline in Non-HDL-C at Week 12 | -0.07 percent change | Standard Error 2.68 |
| A20 Placebo QM | Percent Change From Baseline in Non-HDL-C at Week 12 | -2.38 percent change | Standard Error 2.22 |
| A20 Evolocumab Q2W | Percent Change From Baseline in Non-HDL-C at Week 12 | -68.89 percent change | Standard Error 2.67 |
| A20 Evolocumab QM | Percent Change From Baseline in Non-HDL-C at Week 12 | -63.27 percent change | Standard Error 2.16 |
p-value: <0.00195% CI: [-73.96, -63.89]Repeated measures linear effects model
p-value: <0.00195% CI: [-67.96, -59.21]Repeated measures linear effects model
p-value: <0.00195% CI: [-74.79, -62.86]Repeated measures linear effects model
p-value: <0.00195% CI: [-65.78, -55.99]Repeated measures linear effects model
Secondary
Percent Change From Baseline in the Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in the Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12 | 0.71 percent change | Standard Error 2.11 |
| A5 Placebo QM | Percent Change From Baseline in the Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12 | 4.08 percent change | Standard Error 2.62 |
| A5 Evolocumab Q2W | Percent Change From Baseline in the Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12 | -67.59 percent change | Standard Error 2.16 |
| A5 Evolocumab QM | Percent Change From Baseline in the Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12 | -58.45 percent change | Standard Error 2.53 |
| A20 Placebo Q2W | Percent Change From Baseline in the Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12 | -1.15 percent change | Standard Error 2.47 |
| A20 Placebo QM | Percent Change From Baseline in the Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12 | 0.06 percent change | Standard Error 2.3 |
| A20 Evolocumab Q2W | Percent Change From Baseline in the Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12 | -65.11 percent change | Standard Error 2.46 |
| A20 Evolocumab QM | Percent Change From Baseline in the Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12 | -60.56 percent change | Standard Error 2.23 |
p-value: <0.00195% CI: [-72.75, -63.84]Repeated measures linear effects model
p-value: <0.00195% CI: [-68.11, -56.94]Repeated measures linear effects model
p-value: <0.00195% CI: [-69.44, -58.5]Repeated measures linear effects model
p-value: <0.00195% CI: [-65.51, -55.72]Repeated measures linear effects model
Secondary
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | 3.77 percent change | Standard Error 2.11 |
| A5 Placebo QM | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | 3.94 percent change | Standard Error 2.16 |
| A5 Evolocumab Q2W | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | -51.00 percent change | Standard Error 2.16 |
| A5 Evolocumab QM | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | -48.71 percent change | Standard Error 2.09 |
| A20 Placebo Q2W | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | 1.04 percent change | Standard Error 1.82 |
| A20 Placebo QM | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | 1.58 percent change | Standard Error 2.04 |
| A20 Evolocumab Q2W | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | -49.79 percent change | Standard Error 1.81 |
| A20 Evolocumab QM | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | -48.11 percent change | Standard Error 1.98 |
p-value: <0.00195% CI: [-59.37, -50.17]Repeated measures linear effects model
p-value: <0.00195% CI: [-56.95, -48.36]Repeated measures linear effects model
p-value: <0.00195% CI: [-54.72, -46.93]Repeated measures linear effects model
p-value: <0.00195% CI: [-53.74, -45.64]Repeated measures linear effects model
Secondary
Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 | 4.73 percent change | Standard Error 2.36 |
| A5 Placebo QM | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 | 4.33 percent change | Standard Error 2.33 |
| A5 Evolocumab Q2W | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 | -50.72 percent change | Standard Error 2.4 |
| A5 Evolocumab QM | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 | -46.62 percent change | Standard Error 2.26 |
| A20 Placebo Q2W | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 | 1.84 percent change | Standard Error 2.01 |
| A20 Placebo QM | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 | 0.83 percent change | Standard Error 2.2 |
| A20 Evolocumab Q2W | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 | -49.52 percent change | Standard Error 2 |
| A20 Evolocumab QM | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 | -44.61 percent change | Standard Error 2.13 |
p-value: <0.00195% CI: [-60.93, -49.98]Repeated measures linear effects model
p-value: <0.00195% CI: [-55.91, -46]Repeated measures linear effects model
p-value: <0.00195% CI: [-55.93, -46.8]Repeated measures linear effects model
p-value: <0.00195% CI: [-50.08, -40.81]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 | -2.49 percent change | Standard Error 1.81 |
| A5 Placebo QM | Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 | 1.09 percent change | Standard Error 1.63 |
| A5 Evolocumab Q2W | Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 | -48.03 percent change | Standard Error 1.85 |
| A5 Evolocumab QM | Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 | -42.34 percent change | Standard Error 1.58 |
| A20 Placebo Q2W | Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 | -4.21 percent change | Standard Error 1.86 |
| A20 Placebo QM | Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 | -2.35 percent change | Standard Error 1.68 |
| A20 Evolocumab Q2W | Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 | -45.19 percent change | Standard Error 1.86 |
| A20 Evolocumab QM | Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 | -45.49 percent change | Standard Error 1.63 |
p-value: <0.00195% CI: [-49.35, -41.73]Repeated measures linear effects model
p-value: <0.00195% CI: [-46.78, -40.08]Repeated measures linear effects model
p-value: <0.00195% CI: [-44.88, -37.08]Repeated measures linear effects model
p-value: <0.00195% CI: [-46.48, -39.8]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Total Cholesterol at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in Total Cholesterol at Week 12 | -1.70 percent change | Standard Error 1.97 |
| A5 Placebo QM | Percent Change From Baseline in Total Cholesterol at Week 12 | 2.29 percent change | Standard Error 1.67 |
| A5 Evolocumab Q2W | Percent Change From Baseline in Total Cholesterol at Week 12 | -47.14 percent change | Standard Error 2.01 |
| A5 Evolocumab QM | Percent Change From Baseline in Total Cholesterol at Week 12 | -39.06 percent change | Standard Error 1.62 |
| A20 Placebo Q2W | Percent Change From Baseline in Total Cholesterol at Week 12 | -3.08 percent change | Standard Error 2 |
| A20 Placebo QM | Percent Change From Baseline in Total Cholesterol at Week 12 | -2.44 percent change | Standard Error 1.81 |
| A20 Evolocumab Q2W | Percent Change From Baseline in Total Cholesterol at Week 12 | -44.04 percent change | Standard Error 1.99 |
| A20 Evolocumab QM | Percent Change From Baseline in Total Cholesterol at Week 12 | -40.88 percent change | Standard Error 1.76 |
p-value: <0.00195% CI: [-49.83, -41.05]Repeated measures linear effects model
p-value: <0.00195% CI: [-44.84, -37.85]Repeated measures linear effects model
p-value: <0.00195% CI: [-45.35, -36.57]Repeated measures linear effects model
p-value: <0.00195% CI: [-42.26, -34.62]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | 4.69 percent change | Standard Error 6.04 |
| A5 Placebo QM | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | 4.54 percent change | Standard Error 5.31 |
| A5 Evolocumab Q2W | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | -23.23 percent change | Standard Error 6.15 |
| A5 Evolocumab QM | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | -17.41 percent change | Standard Error 5.14 |
| A20 Placebo Q2W | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | -2.11 percent change | Standard Error 4.45 |
| A20 Placebo QM | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | 8.06 percent change | Standard Error 6.16 |
| A20 Evolocumab Q2W | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | -22.12 percent change | Standard Error 4.44 |
| A20 Evolocumab QM | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | -12.66 percent change | Standard Error 6.01 |
p-value: <0.00195% CI: [-41.27, -14.59]Repeated measures linear effects model
p-value: <0.00195% CI: [-32.54, -11.35]Repeated measures linear effects model
p-value: <0.00195% CI: [-29.59, -10.43]Repeated measures linear effects model
p-value: 0.0195% CI: [-34.18, -7.26]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Triglycerides at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in Triglycerides at Week 12 | 7.84 percent change | Standard Error 7.65 |
| A5 Placebo QM | Percent Change From Baseline in Triglycerides at Week 12 | 4.34 percent change | Standard Error 5.61 |
| A5 Evolocumab Q2W | Percent Change From Baseline in Triglycerides at Week 12 | -19.73 percent change | Standard Error 7.74 |
| A5 Evolocumab QM | Percent Change From Baseline in Triglycerides at Week 12 | -15.63 percent change | Standard Error 5.43 |
| A20 Placebo Q2W | Percent Change From Baseline in Triglycerides at Week 12 | -3.88 percent change | Standard Error 4.85 |
| A20 Placebo QM | Percent Change From Baseline in Triglycerides at Week 12 | 7.30 percent change | Standard Error 6.42 |
| A20 Evolocumab Q2W | Percent Change From Baseline in Triglycerides at Week 12 | -21.05 percent change | Standard Error 4.82 |
| A20 Evolocumab QM | Percent Change From Baseline in Triglycerides at Week 12 | -9.63 percent change | Standard Error 6.26 |
p-value: <0.00195% CI: [-46.33, -8.81]Repeated measures linear effects model
p-value: <0.00195% CI: [-31.68, -8.25]Repeated measures linear effects model
p-value: <0.00195% CI: [-28.15, -6.19]Repeated measures linear effects model
p-value: 0.0195% CI: [-31.29, -2.56]Repeated measures linear effects model
Secondary
Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 | 2.57 percent change | Standard Error 5.52 |
| A5 Placebo QM | Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 | 3.10 percent change | Standard Error 5.12 |
| A5 Evolocumab Q2W | Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 | -25.29 percent change | Standard Error 5.65 |
| A5 Evolocumab QM | Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 | -19.55 percent change | Standard Error 4.95 |
| A20 Placebo Q2W | Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 | -1.32 percent change | Standard Error 4.32 |
| A20 Placebo QM | Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 | 9.96 percent change | Standard Error 5.57 |
| A20 Evolocumab Q2W | Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 | -19.41 percent change | Standard Error 4.31 |
| A20 Evolocumab QM | Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 | -17.20 percent change | Standard Error 5.46 |
p-value: <0.00195% CI: [-39.37, -16.34]Repeated measures linear effects model
p-value: <0.00195% CI: [-32.91, -12.39]Repeated measures linear effects model
p-value: 0.00195% CI: [-27.4, -8.77]Repeated measures linear effects model
p-value: <0.00195% CI: [-39.31, -15.01]Repeated measures linear effects model
Secondary
Percent Change From Baseline in VLDL-C at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A5 Placebo Q2W | Percent Change From Baseline in VLDL-C at Week 12 | 4.09 percent change | Standard Error 6.22 |
| A5 Placebo QM | Percent Change From Baseline in VLDL-C at Week 12 | 2.92 percent change | Standard Error 5.45 |
| A5 Evolocumab Q2W | Percent Change From Baseline in VLDL-C at Week 12 | -24.33 percent change | Standard Error 6.34 |
| A5 Evolocumab QM | Percent Change From Baseline in VLDL-C at Week 12 | -17.89 percent change | Standard Error 5.27 |
| A20 Placebo Q2W | Percent Change From Baseline in VLDL-C at Week 12 | -3.03 percent change | Standard Error 4.7 |
| A20 Placebo QM | Percent Change From Baseline in VLDL-C at Week 12 | 9.17 percent change | Standard Error 5.63 |
| A20 Evolocumab Q2W | Percent Change From Baseline in VLDL-C at Week 12 | -18.08 percent change | Standard Error 4.68 |
| A20 Evolocumab QM | Percent Change From Baseline in VLDL-C at Week 12 | -15.18 percent change | Standard Error 5.52 |
p-value: <0.00195% CI: [-42.48, -14.36]Repeated measures linear effects model
p-value: <0.00195% CI: [-32.29, -9.33]Repeated measures linear effects model
p-value: 0.00195% CI: [-25.72, -4.39]Repeated measures linear effects model
p-value: <0.00195% CI: [-36.7, -11.99]Repeated measures linear effects model