Hyperlipidemia
Conditions
Keywords
High Cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia
Brief summary
The primary objective of this study was to evaluate the effect of 24 weeks of evolocumab administered subcutaneously (SC) every month, compared with ezetimibe, on low-density lipoprotein cholesterol (LDL-C) levels in adults with high cholesterol who are unable to tolerate an effective dose of a statin due to muscle-related side effects (MRSE).
Detailed description
The study is divided into 3 parts (A, B, C). After an initial 4-week washout period in which any statins, ezetimibe, or other lipid-lowering agents were discontinued, participants were enrolled in phase A, a double-blind, placebo-controlled crossover procedure to rechallenge patients with atorvastatin. Patients were randomly assigned in a 1:1 ratio to receive either atorvastatin (20 mg daily) or matching placebo for the first 10 weeks (period 1), then underwent a 2-week washout period, followed by crossover to the alternate therapy for a second 10-week period (period 2). Patients who experienced intolerable muscle symptoms during the first period did not complete the full 10 weeks of exposure but entered a 2-week washout period before proceeding to period 2. Participants who did not develop muscle-related side effects were removed from the study, as were patients who reported muscle-related side effects during a placebo period. After completion of phase A, patients who experienced muscle-related adverse effects while taking atorvastatin but not placebo were eligible for phase B, a 24-week, double-blind randomization to ezetimibe or evolocumab using a double-dummy design in which patients received either injectable placebo and oral ezetimibe or injectable evolocumab and oral placebo. A patient could proceed directly to phase B if they had a documented history of creatine kinase (CK) elevation more than 10 times the upper limit of normal accompanied by muscle symptoms while taking statin therapy, with documented resolution of both CK elevation and symptoms upon discontinuation of statin therapy. These study procedures were designed to ensure that only patients with reproducible statin-associated muscle symptoms entered phase B of the study. For phase B, participants were randomized 2:1 to receive subcutaneously administered evolocumab (420 mg monthly) or oral ezetimibe (10 mg daily). Randomization in part B was stratified by screening LDL-C level (\< 180 mg/dL \[4.66 mmol/L\] vs. ≥ 180 mg/dL) at study baseline. Participants who completed phase B and did not discontinue SC investigational product for any reason, including an adverse event, were eligible to proceed to the 2-year open-label extension phase C to evaluate the long-term safety and efficacy of evolocumab in statin-intolerant patients. Participants in phase C were allowed to choose quarterly between evolocumab 420 mg SC QM or evolocumab 140 mg SC every 2 weeks (Q2W).
Interventions
DRUGAtorvastatin
Atorvastatin was supplied as over-encapsulated 20 mg tablets
Placebo matching to atorvastatin supplied as over-encapsulated tablets
OTHERPlacebo to Ezetimibe
Placebo matching to Ezetimibe supplied as over-encapsulated tablets.
DRUGEzetimibe
Ezetimibe was supplied as 10 mg tablets, over-encapsulated for blinding.
Placebo matching to evolocumab supplied as single-use prefilled autoinjector/pen(s)
DRUGEvolocumab
Evolocumab supplied as single-use prefilled autoinjector/pen(s)
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 * Subject not at LDL-C goal * History of statin intolerance * Lipid lowering therapy has been stable prior to enrolment for at least 4 weeks * Fasting triglycerides ≤ 400 mg/dL
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 LDL-C at the Mean of Weeks 22 and 24 | Baseline and weeks 22 and 24 |
| Percent Change From Baseline in LDL-C at Week 24 | Baseline and week 24 |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants Who Achieved a Mean LDL-C at Weeks 22 and 24 of Less Than 70 mg/dL | Weeks 22 and 24 |
| Percentage of Participants Who Achieved LDL-C at Week 24 of Less Than 70 mg/dL | Week 24 |
| Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 22 and 24 | Baseline and weeks 22 and 24 |
| Percent Change From Baseline in Total Cholesterol at Week 24 | Baseline and week 24 |
| Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 22 and 24 | Baseline and weeks 22 and 24 |
| Percent Change From Baseline in Non-HDL-C at Week 24 | Baseline and week 24 |
| Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 22 and 24 | Baseline and weeks 22 and 24 |
| Percent Change From Baseline in Apolipoprotein B at Week 24 | Baseline and week 24 |
| Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at the Mean of Weeks 22 and 24 | Baseline and weeks 22 and 24 |
| Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 24 | Baseline and week 24 |
| Change From Baseline in LDL-C at the Mean of Weeks 22 and 24 | Baselie and weeks 22 and 24 |
| Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 24 | Baseline and week 24 |
| Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 22 and 24 | Baseline and Weeks 22 and 24 |
| Percent Change From Baseline in Lipoprotein(a) at Week 24 | Baseline and week 24 |
| Percent Change From Baseline in Triglycerides at the Mean of Weeks 22 and 24 | Baseline and weeks 22 and 24 |
| Percent Change From Baseline in Triglycerides at Week 24 | Baseline and week 24 |
| Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 24 | Baseline and weeks 22 and 24 |
| Percent Change From Baseline in HDL-C at Week 24 | Baseline and week 24 |
| Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 22 and 24 | Baseline and weeks 22 and 24 |
| Percent Change From Baseline in VLDL-C at Week 24 | Baseline and week 24 |
| Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 22 and 24 | Baseline and Weeks 22 and 24 |
| Change From Baseline in LDL-C at Week 24 | Baseline and week 24 |
Countries
Australia, Canada, Czechia, Denmark, France, Germany, Italy, Netherlands, New Zealand, Norway, South Africa, United Kingdom, United States
Participant flow
Recruitment details
A total of 511 participants were enrolled (492 in Part A and 19 directly in Part B) at 53 centers in the United States of America, Europe, Australia, New Zealand, Canada, and South Africa from December 2013 to November 2014. Results are reported for participants randomized in Part B. Part C was ongoing at the time of this analysis.
Pre-assignment details
A total of 492 patients were randomized in part A; of those, 202 completed both periods and experienced muscle-related side effects during the atorvastatin period and not during the placebo period. Of the 202, 199 enrolled in Part B. Nineteen additional patients bypassed part A, as permitted by protocol, and advanced directly into part B.
Participants by arm
| Arm | Count |
|---|---|
| Ezetimibe Participants received 10 mg ezetimibe orally once a day and placebo to evolocumab by subcutaneous injection once a month for 24 weeks. | 73 |
| Evolocumab Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo to ezetimibe orally once a day for 24 weeks. | 145 |
| Total | 218 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Sponsor Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 5 |
Baseline characteristics
| Characteristic | Total | Ezetimibe | Evolocumab |
|---|---|---|---|
| Age, Continuous | 58.8 years STANDARD_DEVIATION 10.5 | 58.5 years STANDARD_DEVIATION 9.4 | 59.0 years STANDARD_DEVIATION 11.1 |
| Age, Customized < 65 years | 144 Participants | 52 Participants | 92 Participants |
| Age, Customized ≥ 65 years | 74 Participants | 21 Participants | 53 Participants |
| Apolipoprotein B/Apolipoprotein A1 Ratio | 1.063 ratio STANDARD_DEVIATION 0.366 | 1.063 ratio STANDARD_DEVIATION 0.416 | 1.063 ratio STANDARD_DEVIATION 0.34 |
| Apolipoprotein B Concentration | 157.2 mg/dL STANDARD_DEVIATION 41.7 | 155.0 mg/dL STANDARD_DEVIATION 42.4 | 158.3 mg/dL STANDARD_DEVIATION 41.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 216 Participants | 73 Participants | 143 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| High-density Lipoprotein Cholesterol (HDL-C) | 49.8 mg/dL STANDARD_DEVIATION 15.4 | 50.2 mg/dL STANDARD_DEVIATION 15.5 | 49.7 mg/dL STANDARD_DEVIATION 15.4 |
| LDL-C Concentation | 219.9 mg/dL STANDARD_DEVIATION 72 | 221.9 mg/dL STANDARD_DEVIATION 70.2 | 218.8 mg/dL STANDARD_DEVIATION 73.1 |
| Lipoprotein(a) Concentration | 31.0 nmol/L | 38.0 nmol/L | 29.0 nmol/L |
| Non-high-density Lipoprotein Cholesterol (non-HDL-C) Concentration | 257.2 mg/dL STANDARD_DEVIATION 74.5 | 257.8 mg/dL STANDARD_DEVIATION 76.3 | 256.9 mg/dL STANDARD_DEVIATION 73.8 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 207 Participants | 69 Participants | 138 Participants |
| Sex: Female, Male Female | 106 Participants | 39 Participants | 67 Participants |
| Sex: Female, Male Male | 112 Participants | 34 Participants | 78 Participants |
| Stratification Factor: Screening Low-density Lipoprotein Cholesterol (LDL-C) < 180 mg/dL | 61 Participants | 21 Participants | 40 Participants |
| Stratification Factor: Screening Low-density Lipoprotein Cholesterol (LDL-C) ≥ 180 mg/dL | 157 Participants | 52 Participants | 105 Participants |
| Total Cholesterol Concentration | 307.0 mg/dL STANDARD_DEVIATION 74.7 | 308.0 mg/dL STANDARD_DEVIATION 73.8 | 306.5 mg/dL STANDARD_DEVIATION 75.4 |
| Total Cholesterol/HDL-C Ratio | 6.682 ratio STANDARD_DEVIATION 2.483 | 6.709 ratio STANDARD_DEVIATION 2.746 | 6.668 ratio STANDARD_DEVIATION 2.349 |
| Triglyceride Concentration | 171.3 mg/dL | 162.5 mg/dL | 176.0 mg/dL |
| Very Low-density Lipoprotein Cholesterol (VLDL-C) Concentration | 36.7 mg/dL STANDARD_DEVIATION 15.1 | 35.7 mg/dL STANDARD_DEVIATION 14.3 | 37.1 mg/dL STANDARD_DEVIATION 15.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 80 / 145 | 40 / 73 |
| serious Total, serious adverse events | 9 / 145 | 10 / 73 |
Outcome results
Primary
Percent Change From Baseline in LDL-C at the Mean of Weeks 22 and 24
Time frame: Baseline and weeks 22 and 24
Population: Participants randomized and dosed in part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in LDL-C at the Mean of Weeks 22 and 24 | -16.70 percent change | Standard Error 1.91 |
| Evolocumab | Percent Change From Baseline in LDL-C at the Mean of Weeks 22 and 24 | -54.50 percent change | Standard Error 1.39 |
Comparison: The null hypothesis was that there was no mean difference in the percent change from baseline at week 24 of part B or in the mean percent change from baseline at weeks 22 and 24 of part B in LDL-C between evolocumab 420 mg and ezetimibe, and the alternative hypothesis was that a mean difference did exist.p-value: <0.000195% CI: [-42.31, -33.28]Repeated Measures Model
Primary
Percent Change From Baseline in LDL-C at Week 24
Time frame: Baseline and week 24
Population: Participants randomized and dosed in part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in LDL-C at Week 24 | -16.69 percent change | Standard Error 2.11 |
| Evolocumab | Percent Change From Baseline in LDL-C at Week 24 | -52.76 percent change | Standard Error 1.52 |
Comparison: The null hypothesis was that there was no mean difference in the percent change from baseline at week 24 of part B or in the mean percent change from baseline at weeks 22 and 24 of part B in LDL-C between evolocumab 420 mg and ezetimibe, and the alternative hypothesis was that a mean difference did exist.p-value: <0.000195% CI: [-41.07, -31.08]Repeated Measures Model
Secondary
Change From Baseline in LDL-C at the Mean of Weeks 22 and 24
Time frame: Baselie and weeks 22 and 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Change From Baseline in LDL-C at the Mean of Weeks 22 and 24 | -31.0 mg/dL | Standard Error 3.8 |
| Evolocumab | Change From Baseline in LDL-C at the Mean of Weeks 22 and 24 | -106.8 mg/dL | Standard Error 2.7 |
p-value: <0.000195% CI: [-84.7, -67]Repeated Measures Model
Secondary
Change From Baseline in LDL-C at Week 24
Time frame: Baseline and week 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Change From Baseline in LDL-C at Week 24 | -31.2 mg/dL | Standard Error 4 |
| Evolocumab | Change From Baseline in LDL-C at Week 24 | -102.9 mg/dL | Standard Error 2.9 |
p-value: <0.000195% CI: [-81.3, -62.2]Repeated Measures Model
Secondary
Percentage of Participants Who Achieved a Mean LDL-C at Weeks 22 and 24 of Less Than 70 mg/dL
Time frame: Weeks 22 and 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ezetimibe | Percentage of Participants Who Achieved a Mean LDL-C at Weeks 22 and 24 of Less Than 70 mg/dL | 1.4 percentage of participants |
| Evolocumab | Percentage of Participants Who Achieved a Mean LDL-C at Weeks 22 and 24 of Less Than 70 mg/dL | 29.9 percentage of participants |
p-value: <0.000195% CI: [19.1, 36.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Achieved LDL-C at Week 24 of Less Than 70 mg/dL
Time frame: Week 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ezetimibe | Percentage of Participants Who Achieved LDL-C at Week 24 of Less Than 70 mg/dL | 0.0 percentage of participants |
| Evolocumab | Percentage of Participants Who Achieved LDL-C at Week 24 of Less Than 70 mg/dL | 27.4 percentage of participants |
p-value: <0.000195% CI: [17.7, 36.1]Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 22 and 24
Time frame: Baseline and Weeks 22 and 24
Population: Participants randomized and dosed in Part B of the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 22 and 24 | -11.86 percent change | Standard Error 1.89 |
| Evolocumab | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 22 and 24 | -45.99 percent change | Standard Error 1.36 |
p-value: <0.000195% CI: [-38.59, -29.67]Repeated Measures Model
Secondary
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 24
Time frame: Baseline and week 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 24 | -12.62 percent change | Standard Error 1.97 |
| Evolocumab | Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 24 | -44.60 percent change | Standard Error 1.41 |
p-value: <0.000195% CI: [-36.64, -27.32]Repeated Measures Model
Secondary
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 22 and 24
Time frame: Baseline and weeks 22 and 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 22 and 24 | -11.42 percent change | Standard Error 1.82 |
| Evolocumab | Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 22 and 24 | -45.28 percent change | Standard Error 1.31 |
p-value: <0.000195% CI: [-38.15, -29.58]Repeated Measures Model
Secondary
Percent Change From Baseline in Apolipoprotein B at Week 24
Time frame: Baseline and week 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Apolipoprotein B at Week 24 | -11.74 percent change | Standard Error 1.94 |
| Evolocumab | Percent Change From Baseline in Apolipoprotein B at Week 24 | -43.50 percent change | Standard Error 1.4 |
p-value: <0.000195% CI: [-36.35, -27.16]Repeated Measures Model
Secondary
Percent Change From Baseline in HDL-C at Week 24
Time frame: Baseline and week 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in HDL-C at Week 24 | 2.90 percent change | Standard Error 1.89 |
| Evolocumab | Percent Change From Baseline in HDL-C at Week 24 | 7.40 percent change | Standard Error 1.36 |
p-value: 0.008395% CI: [0.02, 8.98]Repeated Measures Model
Secondary
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 24
Time frame: Baseline and weeks 22 and 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 24 | 1.66 percent change | Standard Error 1.71 |
| Evolocumab | Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 24 | 7.85 percent change | Standard Error 1.24 |
p-value: 0.008395% CI: [2.15, 10.22]Repeated Measures Model
Secondary
Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 22 and 24
Time frame: Baseline and Weeks 22 and 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 22 and 24 | -1.63 percent change | Standard Error 2.8 |
| Evolocumab | Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 22 and 24 | -22.71 percent change | Standard Error 2.03 |
p-value: <0.000195% CI: [-27.65, -14.51]Repeated Measures Model
Secondary
Percent Change From Baseline in Lipoprotein(a) at Week 24
Time frame: Baseline and week 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Lipoprotein(a) at Week 24 | 0.17 percent change | Standard Error 3.05 |
| Evolocumab | Percent Change From Baseline in Lipoprotein(a) at Week 24 | -21.06 percent change | Standard Error 2.19 |
p-value: <0.000195% CI: [-28.42, -14.05]Repeated Measures Model
Secondary
Percent Change From Baseline in Non-HDL-C at Week 24
Time frame: Baseline and week 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Non-HDL-C at Week 24 | -14.62 percent change | Standard Error 1.83 |
| Evolocumab | Percent Change From Baseline in Non-HDL-C at Week 24 | -45.72 percent change | Standard Error 1.32 |
p-value: <0.000195% CI: [-35.44, -16.76]Repeated Measures Model
Secondary
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 22 and 24
Time frame: Baseline and weeks 22 and 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 22 and 24 | -14.38 percent change | Standard Error 1.72 |
| Evolocumab | Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 22 and 24 | -47.44 percent change | Standard Error 1.25 |
p-value: <0.000195% CI: [-37.12, -28.99]Repeated Measures Model
Secondary
Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 22 and 24
Time frame: Baseline and weeks 22 and 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 22 and 24 | -11.43 percent change | Standard Error 1.41 |
| Evolocumab | Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 22 and 24 | -38.04 percent change | Standard Error 1.03 |
p-value: <0.000195% CI: [-29.95, -23.27]Repeated Measures Model
Secondary
Percent Change From Baseline in Total Cholesterol at Week 24
Time frame: Baseline and week 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Total Cholesterol at Week 24 | -11.57 percent change | Standard Error 1.52 |
| Evolocumab | Percent Change From Baseline in Total Cholesterol at Week 24 | -36.64 percent change | Standard Error 1.1 |
p-value: <0.000195% CI: [-28.67, -21.48]Repeated Measures Model
Secondary
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at the Mean of Weeks 22 and 24
Time frame: Baseline and weeks 22 and 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at the Mean of Weeks 22 and 24 | -11.48 percent change | Standard Error 1.75 |
| Evolocumab | Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at the Mean of Weeks 22 and 24 | -41.39 percent change | Standard Error 1.27 |
p-value: <0.000195% CI: [-34.06, -25.77]Repeated Measures Model
Secondary
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 24
Time frame: Baseline and week 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 24 | -12.84 percent change | Standard Error 1.85 |
| Evolocumab | Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 24 | -40.04 percent change | Standard Error 1.33 |
p-value: <0.000195% CI: [-31.58, -22.82]Repeated Measures Model
Secondary
Percent Change From Baseline in Triglycerides at the Mean of Weeks 22 and 24
Time frame: Baseline and weeks 22 and 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Triglycerides at the Mean of Weeks 22 and 24 | -0.95 percent change | Standard Error 3.94 |
| Evolocumab | Percent Change From Baseline in Triglycerides at the Mean of Weeks 22 and 24 | -5.39 percent change | Standard Error 2.84 |
p-value: 0.3795% CI: [-13.74, 4.87]Repeated Measures Model
Secondary
Percent Change From Baseline in Triglycerides at Week 24
Time frame: Baseline and week 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Triglycerides at Week 24 | -1.07 percent change | Standard Error 4.97 |
| Evolocumab | Percent Change From Baseline in Triglycerides at Week 24 | -2.88 percent change | Standard Error 3.54 |
p-value: 0.3795% CI: [-13.64, 10.01]Repeated Measures Model
Secondary
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 22 and 24
Time frame: Baseline and weeks 22 and 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 22 and 24 | -2.15 percent change | Standard Error 3.22 |
| Evolocumab | Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 22 and 24 | -6.81 percent change | Standard Error 2.33 |
p-value: 0.3795% CI: [-12.25, 2.94]Repeated Measures Model
Secondary
Percent Change From Baseline in VLDL-C at Week 24
Time frame: Baseline and week 24
Population: Participants randomized and dosed in Part B of the study
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | Percent Change From Baseline in VLDL-C at Week 24 | -2.66 percent change | Standard Error 3.88 |
| Evolocumab | Percent Change From Baseline in VLDL-C at Week 24 | -3.90 percent change | Standard Error 2.78 |
p-value: 0.3795% CI: [-10.45, 7.98]Repeated Measures Model