Diabetes, Hyperlipidemia, Mixed Dyslipidemia
Conditions
Brief summary
The primary objective of this study was to evaluate the effect of 12 weeks of subcutaneous evolocumab (AMG 145) in combination with statin therapy (atorvastatin) on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in diabetic adults with hyperlipidemia or mixed dyslipidemia.
Interventions
BIOLOGICALEvolocumab
Administered by subcutaneous injection
DRUGAtorvastatin
Administered orally once a day
OTHERPlacebo
Placebo to evolocumab 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
* Males and females with type 2 diabetes (receiving pharmacologic treatment for at least 6 months or longer) with stable diabetes therapy * Lipid-lowering therapy must be unchanged for at least 4 weeks or more * Subjects receiving statin therapy at screening must have a fasting LDL-C of greater than or equal to 100 mg/dL * Subjects not receiving statin therapy at screening must have a fasting LDL-C of greater than or equal to 130 mg/dL
Exclusion criteria
* New York Heart Association (NYHA) class III or IV heart failure * Uncontrolled cardiac arrhythmia * Uncontrolled hypertension * Type 1 diabetes or 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 10 and 12 | Baseline and weeks 10 and 12 |
| Percent Change From Baseline in LDL-C at Week 12 | Baseline and week 12 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 B100 at the Mean of Weeks 10 and 12 | Baseline and weeks 10 and 12 |
| Percent Change From Baseline in Apolipoprotein B100 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 Total Cholesterol at Week 12 | Baseline and week 12 |
| Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | Baseline and weeks 10 and 12 |
| Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12 | Baseline and week 12 |
| Percent Change From Baseline in Apolipoprotein B100/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 | Baseline and weeks 10 and 12 |
| Percent Change From Baseline in Apolipoprotein B100/Apolipoprotein A1 Ratio 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 Less Than 70 mg/dL (1.8 mmol/L) 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 Lipoprotein(a) at Week 12 | Baseline and week 12 |
| 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 Triglycerides at the Mean of Weeks 10 and 12 | Baseline and weeks 10 and 12 |
Countries
Argentina, Brazil, Canada, China, Colombia, France, Russia, South Korea, Turkey (Türkiye), United States
Participant flow
Recruitment details
Participants were enrolled at 102 study centers and randomized at 98 centers in Argentina, Brazil, Canada, China, Colombia, France, Republic of Korea, Russian Federation, Turkey, and the United States from 14 April 2016 to 28 July 2017.
Pre-assignment details
Participants who met eligibility criteria and completed at least 4 weeks of lipid stabilization on atorvastatin 20 mg daily were randomized in a 1:1:2:2 ratio to receive placebo every 2 weeks (Q2W), placebo once a month (QM), evolocumab Q2W, or evolocumab QM. Randomization was stratified by entry statin therapy and geographic region.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Q2W Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and 20 mg atorvastatin orally once a day for up to 12 weeks. | 166 |
| Placebo QM Participants received placebo subcutaneous injection once a month (QM) and 20 mg atorvastatin orally once a day for up to 12 weeks. | 161 |
| Evolocumab Q2W Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and 20 mg atorvastatin orally once a day for up to 12 weeks. | 327 |
| Evolocumab QM Participants received 420 mg evolocumab by subcutaneous injection once a month and 20 mg atorvastatin orally once a day for up to 12 weeks. | 332 |
| Total | 986 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 1 | 6 | 4 |
Baseline characteristics
| Characteristic | Evolocumab Q2W | Placebo Q2W | Placebo QM | Evolocumab QM | Total |
|---|---|---|---|---|---|
| Age, Continuous | 61.0 years STANDARD_DEVIATION 8.5 | 61.6 years STANDARD_DEVIATION 8.8 | 61.0 years STANDARD_DEVIATION 8.8 | 61.6 years STANDARD_DEVIATION 8.4 | 61.3 years STANDARD_DEVIATION 8.6 |
| Age, Customized 18 - 64 years | 206 Participants | 105 Participants | 101 Participants | 208 Participants | 620 Participants |
| Age, Customized 65 - 80 years | 121 Participants | 61 Participants | 60 Participants | 124 Participants | 366 Participants |
| Apolipoprotein B100/Apolipoprotein A1 Ratio | 0.601 ratio STANDARD_DEVIATION 0.2 | 0.573 ratio STANDARD_DEVIATION 0.192 | 0.563 ratio STANDARD_DEVIATION 0.161 | 0.586 ratio STANDARD_DEVIATION 0.185 | 0.585 ratio STANDARD_DEVIATION 0.188 |
| Apolipoprotein B100 Concentration | 84.8 mg/dL STANDARD_DEVIATION 23 | 82.1 mg/dL STANDARD_DEVIATION 23.1 | 83.4 mg/dL STANDARD_DEVIATION 22.3 | 84.4 mg/dL STANDARD_DEVIATION 21.8 | 84.0 mg/dL STANDARD_DEVIATION 22.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 65 Participants | 29 Participants | 34 Participants | 67 Participants | 195 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 262 Participants | 137 Participants | 127 Participants | 265 Participants | 791 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| High-density Lipoprotein Cholesterol (HDL-C) Concentration | 46.5 mg/dL STANDARD_DEVIATION 11.5 | 47.3 mg/dL STANDARD_DEVIATION 11.9 | 49.9 mg/dL STANDARD_DEVIATION 15.2 | 47.6 mg/dL STANDARD_DEVIATION 12.3 | 47.6 mg/dL STANDARD_DEVIATION 12.6 |
| Lipoprotein (a) | 65.6 nmol/L STANDARD_DEVIATION 92.5 | 67.0 nmol/L STANDARD_DEVIATION 90.9 | 71.8 nmol/L STANDARD_DEVIATION 96.5 | 73.2 nmol/L STANDARD_DEVIATION 95.9 | 69.4 nmol/L STANDARD_DEVIATION 94 |
| Low-density Lipoprotein Cholesterol (LDL-C) Concentration | 92.4 mg/dL STANDARD_DEVIATION 33.8 | 92.2 mg/dL STANDARD_DEVIATION 32 | 91.0 mg/dL STANDARD_DEVIATION 30.7 | 93.5 mg/dL STANDARD_DEVIATION 33.6 | 92.5 mg/dL STANDARD_DEVIATION 32.9 |
| Non-high-density Lipoprotein Cholesterol (non-HDL-C) Concentration | 121.3 mg/dL STANDARD_DEVIATION 38.1 | 119.2 mg/dL STANDARD_DEVIATION 38.2 | 119.4 mg/dL STANDARD_DEVIATION 36 | 121.2 mg/dL STANDARD_DEVIATION 37 | 120.6 mg/dL STANDARD_DEVIATION 37.4 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 164 Participants | 82 Participants | 80 Participants | 166 Participants | 492 Participants |
| Race/Ethnicity, Customized Black or African American | 11 Participants | 7 Participants | 6 Participants | 18 Participants | 42 Participants |
| Race/Ethnicity, Customized Multiple | 11 Participants | 5 Participants | 6 Participants | 8 Participants | 30 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 140 Participants | 72 Participants | 68 Participants | 140 Participants | 420 Participants |
| Sex: Female, Male Female | 178 Participants | 102 Participants | 94 Participants | 190 Participants | 564 Participants |
| Sex: Female, Male Male | 149 Participants | 64 Participants | 67 Participants | 142 Participants | 422 Participants |
| Stratification Factor: Geographic Region China | 150 Participants | 76 Participants | 75 Participants | 152 Participants | 453 Participants |
| Stratification Factor: Geographic Region Other countries | 163 Participants | 84 Participants | 81 Participants | 167 Participants | 495 Participants |
| Stratification Factor: Geographic Region South Korea | 14 Participants | 6 Participants | 5 Participants | 13 Participants | 38 Participants |
| Stratification Factor: Statin Therapy at Study Entry Intensive statin usage | 31 Participants | 16 Participants | 15 Participants | 32 Participants | 94 Participants |
| Stratification Factor: Statin Therapy at Study Entry Non-intensive statin usage | 167 Participants | 83 Participants | 80 Participants | 166 Participants | 496 Participants |
| Stratification Factor: Statin Therapy at Study Entry No statin | 129 Participants | 67 Participants | 66 Participants | 134 Participants | 396 Participants |
| Total Cholesterol | 167.8 mg/dL STANDARD_DEVIATION 38.9 | 166.5 mg/dL STANDARD_DEVIATION 38.6 | 169.3 mg/dL STANDARD_DEVIATION 37.5 | 168.9 mg/dL STANDARD_DEVIATION 38.9 | 168.2 mg/dL STANDARD_DEVIATION 38.6 |
| Total Cholesterol/High-density Lipoprotein Cholesterol(HDL-C) Ratio | 3.804 ratio STANDARD_DEVIATION 1.273 | 3.717 ratio STANDARD_DEVIATION 1.337 | 3.598 ratio STANDARD_DEVIATION 1.071 | 3.725 ratio STANDARD_DEVIATION 1.201 | 3.729 ratio STANDARD_DEVIATION 1.229 |
| Triglycerides Concentration | 145.9 mg/dL STANDARD_DEVIATION 67.5 | 137.3 mg/dL STANDARD_DEVIATION 77.3 | 150.6 mg/dL STANDARD_DEVIATION 154.6 | 139.7 mg/dL STANDARD_DEVIATION 64.9 | 143.1 mg/dL STANDARD_DEVIATION 88.4 |
| Very Low-density Lipoprotein Cholesterol (VLDL-C) Concentration | 28.7 mg/dL STANDARD_DEVIATION 12.6 | 27.3 mg/dL STANDARD_DEVIATION 14.9 | 28.4 mg/dL STANDARD_DEVIATION 16.2 | 27.8 mg/dL STANDARD_DEVIATION 12.7 | 28.1 mg/dL STANDARD_DEVIATION 13.7 |
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 | 0 / 164 | 0 / 160 | 0 / 325 | 0 / 332 |
| other Total, other adverse events | 28 / 164 | 22 / 160 | 45 / 325 | 49 / 332 |
| serious Total, serious adverse events | 6 / 164 | 5 / 160 | 10 / 325 | 22 / 332 |
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 | 4.94 percent change | Standard Error 3.48 |
| Placebo QM | Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | 0.99 percent change | Standard Error 3.31 |
| Evolocumab Q2W | Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -65.35 percent change | Standard Error 3.09 |
| Evolocumab QM | Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -69.05 percent change | Standard Error 2.96 |
p-value: <0.000195% CI: [-75.43, -65.16]Repeated measures linear effects model
p-value: <0.000195% CI: [-74.67, -65.41]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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in LDL-C at Week 12 | 7.10 percent change | Standard Error 3.66 |
| Placebo QM | Percent Change From Baseline in LDL-C at Week 12 | 2.63 percent change | Standard Error 3.41 |
| Evolocumab Q2W | Percent Change From Baseline in LDL-C at Week 12 | -64.66 percent change | Standard Error 3.2 |
| Evolocumab QM | Percent Change From Baseline in LDL-C at Week 12 | -62.30 percent change | Standard Error 3.02 |
p-value: <0.000195% CI: [-77.61, -65.93]Repeated measures linear effects model
p-value: <0.000195% CI: [-69.97, -59.89]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 | -2.1 mg/dL | Standard Error 4.1 |
| Placebo QM | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -8.8 mg/dL | Standard Error 4 |
| Evolocumab Q2W | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -64.6 mg/dL | Standard Error 3.6 |
| Evolocumab QM | Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 | -71.9 mg/dL | Standard Error 3.6 |
p-value: <0.000195% CI: [-68.2, -56.9]Repeated measures linear effects model
p-value: <0.000195% CI: [-68.4, -57.8]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 | -0.3 mg/dL | Standard Error 4.2 |
| Placebo QM | Change From Baseline in LDL-C at Week 12 | -7.3 mg/dL | Standard Error 4.1 |
| Evolocumab Q2W | Change From Baseline in LDL-C at Week 12 | -63.9 mg/dL | Standard Error 3.7 |
| Evolocumab QM | Change From Baseline in LDL-C at Week 12 | -66.1 mg/dL | Standard Error 3.7 |
p-value: <0.000195% CI: [-69.7, -57.6]Repeated measures linear effects model
p-value: <0.000195% CI: [-64.3, -53.3]Repeated measures linear effects model
Secondary
Percentage of Participants With LDL-C Less Than 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 Less Than 70 mg/dL (1.8 mmol/L) at Week 12 | 20.9 percentage of participants |
| Placebo QM | Percentage of Participants With LDL-C Less Than 70 mg/dL (1.8 mmol/L) at Week 12 | 21.3 percentage of participants |
| Evolocumab Q2W | Percentage of Participants With LDL-C Less Than 70 mg/dL (1.8 mmol/L) at Week 12 | 88.2 percentage of participants |
| Evolocumab QM | Percentage of Participants With LDL-C Less Than 70 mg/dL (1.8 mmol/L) at Week 12 | 90.2 percentage of participants |
p-value: <0.000195% CI: [58.9, 73.9]Cochran-Mantel-Haenszel
p-value: <0.000195% CI: [60.6, 75.3]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) | 21.7 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) | 19.4 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) | 90.1 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) | 91.3 percentage of participants |
p-value: <0.000195% CI: [60.4, 74.8]Cochran-Mantel-Haenszel
p-value: <0.000195% CI: [64.1, 77.9]Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in Apolipoprotein B100/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 B100/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 | 2.60 percent change | Standard Error 3.3 |
| Placebo QM | Percent Change From Baseline in Apolipoprotein B100/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 | -1.02 percent change | Standard Error 3.09 |
| Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B100/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 | -55.60 percent change | Standard Error 3.07 |
| Evolocumab QM | Percent Change From Baseline in Apolipoprotein B100/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12 | -57.75 percent change | Standard Error 2.82 |
p-value: <0.000195% CI: [-62.15, -54.25]Repeated measures linear effects model
p-value: <0.000195% CI: [-60.53, -52.93]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Apolipoprotein B100/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 B100/Apolipoprotein A1 Ratio at Week 12 | 3.23 percent change | Standard Error 3.39 |
| Placebo QM | Percent Change From Baseline in Apolipoprotein B100/Apolipoprotein A1 Ratio at Week 12 | -0.10 percent change | Standard Error 3.16 |
| Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B100/Apolipoprotein A1 Ratio at Week 12 | -54.98 percent change | Standard Error 3.12 |
| Evolocumab QM | Percent Change From Baseline in Apolipoprotein B100/Apolipoprotein A1 Ratio at Week 12 | -51.80 percent change | Standard Error 2.86 |
p-value: <0.000195% CI: [-62.59, -53.84]Repeated measures linear effects model
p-value: <0.000195% CI: [-55.81, -47.59]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Apolipoprotein B100 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 B100 at the Mean of Weeks 10 and 12 | 1.97 percent change | Standard Error 3.31 |
| Placebo QM | Percent Change From Baseline in Apolipoprotein B100 at the Mean of Weeks 10 and 12 | -1.52 percent change | Standard Error 2.99 |
| Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B100 at the Mean of Weeks 10 and 12 | -54.96 percent change | Standard Error 3.07 |
| Evolocumab QM | Percent Change From Baseline in Apolipoprotein B100 at the Mean of Weeks 10 and 12 | -56.37 percent change | Standard Error 2.72 |
p-value: <0.000195% CI: [-60.93, -52.93]Repeated measures linear effects model
p-value: <0.000195% CI: [-58.52, -51.18]Repeated measures linear effects model
Secondary
Percent Change From Baseline in Apolipoprotein B100 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 B100 at Week 12 | 3.17 percent change | Standard Error 3.42 |
| Placebo QM | Percent Change From Baseline in Apolipoprotein B100 at Week 12 | -0.26 percent change | Standard Error 3.03 |
| Evolocumab Q2W | Percent Change From Baseline in Apolipoprotein B100 at Week 12 | -53.90 percent change | Standard Error 3.14 |
| Evolocumab QM | Percent Change From Baseline in Apolipoprotein B100 at Week 12 | -49.68 percent change | Standard Error 2.75 |
p-value: <0.000195% CI: [-61.59, -52.54]Repeated measures linear effects model
p-value: <0.000195% CI: [-53.31, -45.53]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 | 1.25 percent change | Standard Error 2.19 |
| Placebo QM | Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 | 5.88 percent change | Standard Error 2.11 |
| Evolocumab Q2W | Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 | 7.59 percent change | Standard Error 1.99 |
| Evolocumab QM | Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 | 13.75 percent change | Standard Error 1.9 |
p-value: 0.000395% CI: [3.36, 9.33]Repeated measures linear effects model
p-value: <0.000195% CI: [5.1, 10.65]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 | 2.57 percent change | Standard Error 2.29 |
| Placebo QM | Percent Change From Baseline in HDL-C at Week 12 | 6.04 percent change | Standard Error 2.18 |
| Evolocumab Q2W | Percent Change From Baseline in HDL-C at Week 12 | 8.45 percent change | Standard Error 2.04 |
| Evolocumab QM | Percent Change From Baseline in HDL-C at Week 12 | 14.18 percent change | Standard Error 1.95 |
p-value: 0.000395% CI: [2.49, 9.27]Repeated measures linear effects model
p-value: <0.000195% CI: [5.03, 11.25]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 | 16.89 percent change | Standard Error 17.49 |
| Placebo QM | Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12 | 8.48 percent change | Standard Error 9.49 |
| Evolocumab Q2W | Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12 | -38.63 percent change | Standard Error 13.67 |
| Evolocumab QM | Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12 | -42.29 percent change | Standard Error 8.49 |
p-value: <0.000195% CI: [-92.64, -18.4]Repeated measures linear effects model
p-value: <0.000195% CI: [-63.82, -37.72]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 | 26.53 percent change | Standard Error 21.78 |
| Placebo QM | Percent Change From Baseline in Lipoprotein(a) at Week 12 | 7.47 percent change | Standard Error 10.4 |
| Evolocumab Q2W | Percent Change From Baseline in Lipoprotein(a) at Week 12 | -35.93 percent change | Standard Error 16.47 |
| Evolocumab QM | Percent Change From Baseline in Lipoprotein(a) at Week 12 | -37.85 percent change | Standard Error 9.02 |
p-value: <0.000195% CI: [-110.89, -14.03]Repeated measures linear effects model
p-value: <0.000195% CI: [-61.87, -28.77]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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | 4.33 percent change | Standard Error 3.05 |
| Placebo QM | Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | 0.33 percent change | Standard Error 2.95 |
| Evolocumab Q2W | Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | -56.57 percent change | Standard Error 2.7 |
| Evolocumab QM | Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 | -59.08 percent change | Standard Error 2.63 |
p-value: <0.000195% CI: [-65.51, -56.29]Repeated measures linear effects model
p-value: <0.000195% CI: [-63.52, -55.29]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 | 5.87 percent change | Standard Error 3.2 |
| Placebo QM | Percent Change From Baseline in Non-HDL-C at Week 12 | 1.30 percent change | Standard Error 3.03 |
| Evolocumab Q2W | Percent Change From Baseline in Non-HDL-C at Week 12 | -55.76 percent change | Standard Error 2.79 |
| Evolocumab QM | Percent Change From Baseline in Non-HDL-C at Week 12 | -52.92 percent change | Standard Error 2.69 |
p-value: <0.000195% CI: [-66.82, -56.45]Repeated measures linear effects model
p-value: <0.000195% CI: [-58.7, -49.74]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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 | 2.89 percent change | Standard Error 2.3 |
| Placebo QM | Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 | -0.25 percent change | Standard Error 2.18 |
| Evolocumab Q2W | Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 | -38.64 percent change | Standard Error 2.04 |
| Evolocumab QM | Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 | -39.74 percent change | Standard Error 1.95 |
p-value: <0.000195% CI: [-44.95, -38.1]Repeated measures linear effects model
p-value: <0.000195% CI: [-42.47, -36.53]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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in Total Cholesterol at Week 12 | 4.40 percent change | Standard Error 2.4 |
| Placebo QM | Percent Change From Baseline in Total Cholesterol at Week 12 | 0.67 percent change | Standard Error 2.24 |
| Evolocumab Q2W | Percent Change From Baseline in Total Cholesterol at Week 12 | -37.82 percent change | Standard Error 2.1 |
| Evolocumab QM | Percent Change From Baseline in Total Cholesterol at Week 12 | -35.22 percent change | Standard Error 1.99 |
p-value: <0.000195% CI: [-46.02, -38.42]Repeated measures linear effects model
p-value: <0.000195% CI: [-39.12, -32.67]Repeated measures linear effects model
Secondary
Percent Change From Baseline in 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 Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | 3.03 percent change | Standard Error 2.38 |
| Placebo QM | Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | -2.03 percent change | Standard Error 2.41 |
| Evolocumab Q2W | Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | -41.06 percent change | Standard Error 2.11 |
| Evolocumab QM | Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 | -45.70 percent change | Standard Error 2.17 |
p-value: <0.000195% CI: [-47.64, -40.54]Repeated measures linear effects model
p-value: <0.000195% CI: [-46.9, -40.44]Repeated measures linear effects model
Secondary
Percent Change From Baseline in 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 Total Cholesterol/HDL-C Ratio at Week 12 | 3.22 percent change | Standard Error 2.49 |
| Placebo QM | Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12 | -1.22 percent change | Standard Error 2.47 |
| Evolocumab Q2W | Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12 | -40.72 percent change | Standard Error 2.18 |
| Evolocumab QM | Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12 | -41.78 percent change | Standard Error 2.21 |
p-value: <0.000195% CI: [-47.9, -39.97]Repeated measures linear effects model
p-value: <0.000195% CI: [-44.08, -37.04]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 | 11.54 percent change | Standard Error 5.27 |
| Placebo QM | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | 8.48 percent change | Standard Error 4.48 |
| Evolocumab Q2W | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | -6.48 percent change | Standard Error 4.7 |
| Evolocumab QM | Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 | -7.15 percent change | Standard Error 4.02 |
p-value: 0.000295% CI: [-25.89, -10.14]Repeated measures linear effects model
p-value: <0.000195% CI: [-21.69, -9.58]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 | 10.50 percent change | Standard Error 5.36 |
| Placebo QM | Percent Change From Baseline in Triglycerides at Week 12 | 8.07 percent change | Standard Error 4.57 |
| Evolocumab Q2W | Percent Change From Baseline in Triglycerides at Week 12 | -5.91 percent change | Standard Error 4.75 |
| Evolocumab QM | Percent Change From Baseline in Triglycerides at Week 12 | -4.24 percent change | Standard Error 4.09 |
p-value: 0.000295% CI: [-24.63, -8.19]Repeated measures linear effects model
p-value: <0.000195% CI: [-18.76, -5.86]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 |
|---|---|---|---|
| Placebo Q2W | Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 | 9.63 percent change | Standard Error 4.7 |
| Placebo QM | Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 | 7.92 percent change | Standard Error 4.43 |
| Evolocumab Q2W | Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 | -17.55 percent change | Standard Error 4.19 |
| Evolocumab QM | Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 | -16.09 percent change | Standard Error 3.99 |
p-value: <0.000195% CI: [-34.2, -20.17]Repeated measures linear effects model
p-value: <0.000195% CI: [-29.88, -18.14]Repeated measures linear effects model