Hyperlipidemia
Conditions
Keywords
High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia
Brief summary
The primary objective was to evaluate the effect of 12 weeks of evolocumab subcutaneously once every 2 weeks (Q2W) and once monthly (QM), compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in adults with heterozygous familial hypercholesterolemia (HeFH).
Interventions
BIOLOGICALEvolocumab
Administered by subcutaneous injection
DRUGPlacebo
Administered by subcutaneous injection
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male or female ≥ 18 to ≤ 80 years of age * Diagnosis of heterozygous familial hypercholesterolemia * On a stable dose of an approved statin and lipid regulating medication * Fasting LDL-C ≥ 100 mg/dL (2.6 mmol/L) * Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)
Exclusion criteria
* Homozygous familial hypercholesterolemia * LDL or plasma apheresis * 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 LDL-C at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in LDL-C at Week 12 | Baseline and Week 12 |
| Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L) | Weeks 10 and 12 |
| Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12 | Week 12 |
| Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (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 Apolipoprotein B at Week 12 | Baseline and Week 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 VLDL-C at Week 12 | Baseline and Week 12 |
| Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | Baseline and 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 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 Very Low-Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
| Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | Baseline and Weeks 10 and 12 |
Countries
Australia, Canada, France, Germany, Hong Kong, Netherlands, New Zealand, Norway, South Africa, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Men and women 18 to 80 years old with a diagnosis of heterozygous familial hypercholesterolemia (HeFH) on stable doses of an approved statin with fasting low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL were eligible for this study. The first participant enrolled on 07 February 2013 and the last participant enrolled 03 September 2013.
Pre-assignment details
Participants received subcutaneous placebo corresponding to the once monthly dose volume during a 6-week screening period. Those who completed the screening period and met final eligibility criteria were randomized 1:1:2:2 into 4 treatment groups. Randomization was stratified by LDL-C level (\< 160 mg/dL vs ≥ 160 mg/dL) and ezetimibe use.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Q2W Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for up to 12 weeks. | 55 |
| Placebo QM Participants received placebo subcutaneous injection once every month (QM) for up to 12 weeks. | 55 |
| Evolocumab Q2W Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for up to 12 weeks. | 111 |
| Evolocumab QM Participants received 420 mg evolocumab by subcutaneous injection once a month for up to 12 weeks. | 110 |
| Total | 331 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Sponsor Decision | 4 | 0 | 9 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Total | Evolocumab QM | Evolocumab Q2W | Placebo QM | Placebo Q2W |
|---|---|---|---|---|---|
| Age, Continuous | 51.1 years STANDARD_DEVIATION 12.7 | 51.9 years STANDARD_DEVIATION 12 | 52.3 years STANDARD_DEVIATION 12.6 | 46.8 years STANDARD_DEVIATION 12.1 | 51.1 years STANDARD_DEVIATION 14.1 |
| Apolipoprotein B/Apolipoprotein A1 Ratio | 0.857 ratio STANDARD_DEVIATION 0.305 | 0.850 ratio STANDARD_DEVIATION 0.331 | 0.888 ratio STANDARD_DEVIATION 0.322 | 0.851 ratio STANDARD_DEVIATION 0.249 | 0.815 ratio STANDARD_DEVIATION 0.264 |
| Apolipoprotein B Concentration | 115.4 mg/dL STANDARD_DEVIATION 27.5 | 114.9 mg/dL STANDARD_DEVIATION 25.5 | 119.0 mg/dL STANDARD_DEVIATION 30.7 | 110.3 mg/dL STANDARD_DEVIATION 21.7 | 114.3 mg/dL STANDARD_DEVIATION 29.8 |
| Baseline Ezetimibe Use No | 129 participants | 43 participants | 43 participants | 21 participants | 22 participants |
| Baseline Ezetimibe Use Yes | 202 participants | 67 participants | 68 participants | 34 participants | 33 participants |
| HDL-C Concentration | 51.1 mg/dL STANDARD_DEVIATION 15.6 | 51.9 mg/dL STANDARD_DEVIATION 16 | 50.4 mg/dL STANDARD_DEVIATION 16.1 | 49.1 mg/dL STANDARD_DEVIATION 12.7 | 53.2 mg/dL STANDARD_DEVIATION 16.5 |
| LDL-C Concentration | 155.5 mg/dL STANDARD_DEVIATION 44.9 | 153.6 mg/dL STANDARD_DEVIATION 43.3 | 161.4 mg/dL STANDARD_DEVIATION 51 | 151.5 mg/dL STANDARD_DEVIATION 42.5 | 151.1 mg/dL STANDARD_DEVIATION 36.5 |
| Lipoprotein(a) Concentration | 65.0 nmol/L | 61.0 nmol/L | 77.5 nmol/L | 87.0 nmol/L | 44.0 nmol/L |
| Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration | 180.4 mg/dL STANDARD_DEVIATION 49.5 | 178.5 mg/dL STANDARD_DEVIATION 45.8 | 187.4 mg/dL STANDARD_DEVIATION 56.7 | 175.4 mg/dL STANDARD_DEVIATION 45.9 | 175.4 mg/dL STANDARD_DEVIATION 43.9 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 16 participants | 8 participants | 4 participants | 3 participants | 1 participants |
| Race/Ethnicity, Customized Black or African American | 3 participants | 1 participants | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 329 participants | 109 participants | 111 participants | 55 participants | 54 participants |
| Race/Ethnicity, Customized Other | 14 participants | 3 participants | 6 participants | 3 participants | 2 participants |
| Race/Ethnicity, Customized White | 298 participants | 98 participants | 100 participants | 49 participants | 51 participants |
| Sex: Female, Male Female | 140 Participants | 46 Participants | 45 Participants | 24 Participants | 25 Participants |
| Sex: Female, Male Male | 191 Participants | 64 Participants | 66 Participants | 31 Participants | 30 Participants |
| Stratification Factor: Low-Density Lipoprotein Cholesterol (LDL-C) Level < 160 mg/dL | 210 participants | 70 participants | 70 participants | 35 participants | 35 participants |
| Stratification Factor: Low-Density Lipoprotein Cholesterol (LDL-C) Level ≥ 160 mg/dL | 121 participants | 40 participants | 41 participants | 20 participants | 20 participants |
| Total cholesterol/HDL-C Ratio | 4.924 ratio STANDARD_DEVIATION 1.845 | 4.842 ratio STANDARD_DEVIATION 1.801 | 5.159 ratio STANDARD_DEVIATION 2.031 | 4.844 ratio STANDARD_DEVIATION 1.435 | 4.695 ratio STANDARD_DEVIATION 1.905 |
| Triglyceride Concentration | 110.0 mg/dL | 112.5 mg/dL | 118.5 mg/dL | 102.0 mg/dL | 95.8 mg/dL |
| Very Low-Density Lipoprotein Cholesterol (VLDL-C) Concentration | 24.8 mg/dL STANDARD_DEVIATION 11.4 | 24.9 mg/dL STANDARD_DEVIATION 11.7 | 25.9 mg/dL STANDARD_DEVIATION 11.8 | 23.9 mg/dL STANDARD_DEVIATION 10.5 | 23.1 mg/dL STANDARD_DEVIATION 10.7 |
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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 54 | 10 / 55 | 17 / 110 | 24 / 110 |
| serious Total, serious adverse events | 2 / 54 | 3 / 55 | 3 / 110 | 4 / 110 |
Outcome results
Primary
Percent 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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -1.08 percent change | Standard Error 2.41 |
| Placebo QM | Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | 2.30 percent change | Standard Error 2.41 |
| Evolocumab Q2W | Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -61.23 percent change | Standard Error 1.71 |
| Evolocumab QM | Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -63.25 percent change | Standard Error 1.7 |
Comparison: Within each dose frequency, the null hypothesis was that there was no mean difference in the percent change from baseline at week 12 or 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: [-65.83, -54.46]Repeated measures linear effects model
Comparison: Within each dose frequency, the null hypothesis was that there was no mean difference in the percent change from baseline at week 12 or 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: [-71.27, -59.83]Repeated measures linear effects model
Primary
Percent Change From Baseline in LDL-C at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set. Least squares (LS) means are from a repeated measures linear effects model; missing values were not imputed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in LDL-C at Week 12 | -2.02 percent change | Standard Error 2.49 |
| Placebo QM | Percent Change From Baseline in LDL-C at Week 12 | 5.53 percent change | Standard Error 3.25 |
| Evolocumab Q2W | Percent Change From Baseline in LDL-C at Week 12 | -61.25 percent change | Standard Error 1.77 |
| Evolocumab QM | Percent Change From Baseline in LDL-C at Week 12 | -55.74 percent change | Standard Error 2.25 |
Comparison: Within each dose frequency, the null hypothesis was that there was no mean difference in the percent change from baseline at week 12 or 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: [-65.11, -53.35]Repeated measures linear effects model
Comparison: Within each dose frequency, the null hypothesis was that there was no mean difference in the percent change from baseline at week 12 or 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: [-69, -53.55]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 |
|---|---|---|---|
| Placebo Q2W | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -6.5 mg/dL | Standard Error 4.2 |
| Placebo QM | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -1.3 mg/dL | Standard Error 4.1 |
| Evolocumab Q2W | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -101.7 mg/dL | Standard Error 3 |
| Evolocumab QM | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -98.8 mg/dL | Standard Error 2.9 |
p-value: <0.00195% CI: [-105.1, -85.2]Repeated measures linear effects model
p-value: <0.00195% CI: [-107.1, -87.7]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 |
|---|---|---|---|
| Placebo Q2W | Change From Baseline in LDL-C at Week 12 | -8.5 mg/dL | Standard Error 4.2 |
| Placebo QM | Change From Baseline in LDL-C at Week 12 | 4.1 mg/dL | Standard Error 5.2 |
| Evolocumab Q2W | Change From Baseline in LDL-C at Week 12 | -101.3 mg/dL | Standard Error 3 |
| Evolocumab QM | Change From Baseline in LDL-C at Week 12 | -87.2 mg/dL | Standard Error 3.6 |
p-value: <0.00195% CI: [-102.9, -82.8]Repeated measures linear effects model
p-value: <0.00195% CI: [-103.8, -78.9]Repeated measures linear effects model
Secondary
Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12
Time frame: Week 12
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Q2W | Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12 | 2.0 percentage of participants |
| Placebo QM | Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12 | 2.2 percentage of participants |
| Evolocumab Q2W | Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12 | 68.3 percentage of participants |
| Evolocumab QM | Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12 | 63.1 percentage of participants |
p-value: <0.00195% CI: [53.7, 74.6]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [47.6, 69.8]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L)
Time frame: Weeks 10 and 12
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Q2W | Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L) | 1.9 percentage of participants |
| Placebo QM | Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L) | 1.9 percentage of participants |
| Evolocumab Q2W | Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L) | 67.0 percentage of participants |
| Evolocumab QM | Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L) | 80.4 percentage of participants |
p-value: <0.00195% CI: [52.8, 73.4]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [66.9, 85.1]Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 | 0.78 percent change | Standard Error 2.21 |
| Placebo QM | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 | 1.65 percent change | Standard Error 2.35 |
| Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 | -52.39 percent change | Standard Error 1.56 |
| Evolocumab QM | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 | -53.91 percent change | Standard Error 1.6 |
p-value: <0.00195% CI: [-58.35, -47.99]Repeated measures linear effects model
p-value: <0.00195% CI: [-61.08, -50.05]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
Time frame: Baseline and Week 12
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | 1.54 percent change | Standard Error 2.49 |
| Placebo QM | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | 4.23 percent change | Standard Error 3.66 |
| Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | -52.74 percent change | Standard Error 1.75 |
| Evolocumab QM | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 | -45.31 percent change | Standard Error 2.42 |
p-value: <0.00195% CI: [-60.16, -48.41]Repeated measures linear effects model
p-value: <0.00195% CI: [-58.14, -40.96]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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | -0.19 percent change | Standard Error 2.1 |
| Placebo QM | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | 2.21 percent change | Standard Error 1.97 |
| Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | -49.58 percent change | Standard Error 1.48 |
| Evolocumab QM | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 | -52.76 percent change | Standard Error 1.36 |
p-value: <0.00195% CI: [-54.32, -44.46]Repeated measures linear effects model
p-value: <0.00195% CI: [-59.58, -50.38]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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Apolipoprotein B at Week 12 | -0.67 percent change | Standard Error 2.32 |
| Placebo QM | Percent Change From Baseline in Apolipoprotein B at Week 12 | 4.60 percent change | Standard Error 2.7 |
| Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B at Week 12 | -49.75 percent change | Standard Error 1.63 |
| Evolocumab QM | Percent Change From Baseline in Apolipoprotein B at Week 12 | -44.81 percent change | Standard Error 1.8 |
p-value: <0.00195% CI: [-54.55, -43.63]Repeated measures linear effects model
p-value: <0.00195% CI: [-55.73, -43.1]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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 | -0.45 percent change | Standard Error 1.7 |
| Placebo QM | Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 | -2.86 percent change | Standard Error 1.84 |
| Evolocumab Q2W | Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 | 7.93 percent change | Standard Error 1.2 |
| Evolocumab QM | Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 | 6.62 percent change | Standard Error 1.29 |
p-value: <0.00195% CI: [4.36, 12.4]Repeated measures linear effects model
p-value: <0.00195% CI: [5.1, 13.85]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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in HDL-C at Week 12 | -1.15 percent change | Standard Error 1.91 |
| Placebo QM | Percent Change From Baseline in HDL-C at Week 12 | -3.73 percent change | Standard Error 2.35 |
| Evolocumab Q2W | Percent Change From Baseline in HDL-C at Week 12 | 8.05 percent change | Standard Error 1.35 |
| Evolocumab QM | Percent Change From Baseline in HDL-C at Week 12 | 5.35 percent change | Standard Error 1.62 |
p-value: <0.00195% CI: [4.66, 13.74]Repeated measures linear effects model
p-value: <0.00195% CI: [3.48, 1466]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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12 | 7.34 percent change | Standard Error 2.97 |
| Placebo QM | Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12 | 5.35 percent change | Standard Error 2.95 |
| Evolocumab Q2W | Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12 | -24.03 percent change | Standard Error 2.09 |
| Evolocumab QM | Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12 | -25.65 percent change | Standard Error 2.07 |
p-value: <0.00195% CI: [-38.33, -24.41]Repeated measures linear effects model
p-value: <0.00195% CI: [-37.91, -24.09]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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Lipoprotein (a) at Week 12 | 8.68 percent change | Standard Error 3.27 |
| Placebo QM | Percent Change From Baseline in Lipoprotein (a) at Week 12 | 6.69 percent change | Standard Error 3.16 |
| Evolocumab Q2W | Percent Change From Baseline in Lipoprotein (a) at Week 12 | -22.89 percent change | Standard Error 2.31 |
| Evolocumab QM | Percent Change From Baseline in Lipoprotein (a) at Week 12 | -21.55 percent change | Standard Error 2.17 |
p-value: <0.00195% CI: [-39.28, -23.87]Repeated measures linear effects model
p-value: <0.00195% CI: [-35.61, -20.88]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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Non-HDL-C at Week 12 | -1.39 percent change | Standard Error 2.4 |
| Placebo QM | Percent Change From Baseline in Non-HDL-C at Week 12 | 5.29 percent change | Standard Error 2.94 |
| Evolocumab Q2W | Percent Change From Baseline in Non-HDL-C at Week 12 | -56.19 percent change | Standard Error 1.71 |
| Evolocumab QM | Percent Change From Baseline in Non-HDL-C at Week 12 | -49.67 percent change | Standard Error 2.04 |
p-value: <0.00195% CI: [-60.47, -49.12]Repeated measures linear effects model
p-value: <0.00195% CI: [-61.95, -47.96]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12 | 0.21 percent change | Standard Error 2.29 |
| Placebo QM | Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12 | 2.72 percent change | Standard Error 2.21 |
| Evolocumab Q2W | Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12 | -55.79 percent change | Standard Error 1.63 |
| Evolocumab QM | Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12 | -57.28 percent change | Standard Error 1.56 |
p-value: <0.00195% CI: [-61.41, -50.59]Repeated measures linear effects model
p-value: <0.00195% CI: [-65.24, -54.77]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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | 0.86 percent change | Standard Error 2.05 |
| Placebo QM | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | 4.14 percent change | Standard Error 2.13 |
| Evolocumab Q2W | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | -45.74 percent change | Standard Error 1.45 |
| Evolocumab QM | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | -45.02 percent change | Standard Error 1.5 |
p-value: <0.00195% CI: [-51.43, -41.76]Repeated measures linear effects model
p-value: <0.00195% CI: [-54.21, -44.11]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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 | 0.12 percent change | Standard Error 2.19 |
| Placebo QM | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 | 7.11 percent change | Standard Error 3.13 |
| Evolocumab Q2W | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 | -45.95 percent change | Standard Error 1.56 |
| Evolocumab QM | Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 | -38.32 percent change | Standard Error 2.15 |
p-value: <0.00195% CI: [-51.27, -40.88]Repeated measures linear effects model
p-value: <0.00195% CI: [-52.86, -37.98]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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | 9.09 percent change | Standard Error 3.02 |
| Placebo QM | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | 7.49 percent change | Standard Error 3.26 |
| Evolocumab Q2W | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | -13.27 percent change | Standard Error 2.14 |
| Evolocumab QM | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | -9.25 percent change | Standard Error 2.27 |
p-value: <0.00195% CI: [-29.48, -15.24]Repeated measures linear effects model
p-value: <0.00195% CI: [-24.43, -9.05]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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Triglycerides at Week 12 | 3.50 percent change | Standard Error 3.51 |
| Placebo QM | Percent Change From Baseline in Triglycerides at Week 12 | 6.43 percent change | Standard Error 4.15 |
| Evolocumab Q2W | Percent Change From Baseline in Triglycerides at Week 12 | -16.09 percent change | Standard Error 2.49 |
| Evolocumab QM | Percent Change From Baseline in Triglycerides at Week 12 | -5.13 percent change | Standard Error 2.84 |
p-value: <0.00195% CI: [-27.92, -11.26]Repeated measures linear effects model
p-value: <0.00195% CI: [-21.38, -1.74]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12 | 8.66 percent change | Standard Error 2.9 |
| Placebo QM | Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12 | 6.34 percent change | Standard Error 3.27 |
| Evolocumab Q2W | Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12 | -13.97 percent change | Standard Error 2.06 |
| Evolocumab QM | Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12 | -9.20 percent change | Standard Error 2.27 |
p-value: <0.00195% CI: [-29.46, -15.81]Repeated measures linear effects model
p-value: <0.00195% CI: [-23.25, -7.84]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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in VLDL-C at Week 12 | 3.73 percent change | Standard Error 3.5 |
| Placebo QM | Percent Change From Baseline in VLDL-C at Week 12 | 4.10 percent change | Standard Error 4.17 |
| Evolocumab Q2W | Percent Change From Baseline in VLDL-C at Week 12 | -17.25 percent change | Standard Error 2.48 |
| Evolocumab QM | Percent Change From Baseline in VLDL-C at Week 12 | -5.06 percent change | Standard Error 2.84 |
p-value: <0.00195% CI: [-29.29, -12.66]Repeated measures linear effects model
p-value: <0.00195% CI: [-19.01, 0.68]Repeated measures linear effects model