Trial Outcomes & Findings for Pharmacodynamic Biomarkers to Support Biosimilar Development: PCSK9 Inhibitors (NCT NCT04189484)

Last Updated: 2024-04-22

Results Overview

The values and variability of AUEC for LDL-C at low, intermediate-low, intermediate-high, and high doses of evolocumab and alirocumab. AUEC was calculated as the baseline-subtracted area under the LDL-C concentration-time curve expressed in units of mg/(dL\*day). More negative AUEC values represent greater reductions in LDL-C exposure from baseline. The standard deviation is noted in parentheses. For each subject and dose, the maximum decrease from baseline LDL-C was determined using all sampled timepoints. AUEC values were log-transformed and an ANCOVA model was used to calculate geometric means and 90% confidence intervals for each treatment group.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

72 participants

Primary outcome timeframe

Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.

Results posted on

2024-04-22

Participant Flow

Participant milestones

Participant milestones
Measure	Arm A: Evolocumab Low Dose Single dose of evolocumab 21 mg subcutaneous (SC) Evolocumab: Evolocumab 21 mg administered SC	Arm B: Evolocumab Intermediate Low Dose Single dose of evolocumab 35 mg SC Evolocumab: Evolocumab 35 mg administered SC	Arm C: Evolocumab Intermediate High Dose Single dose of evolocumab 70 mg SC Evolocumab: Evolocumab 70 mg administered SC	Arm D: Evolocumab High Dose Single dose of evolocumab 140 mg SC Evolocumab: Evolocumab 140 mg administered SC	Arm E: Alirocumab Low Dose Single dose of alirocumab 15 mg SC Alirocumab: Alirocumab 15 mg administered SC	Arm F: Alirocumab Intermediate Low Dose Single dose of alirocumab 25 mg SC Alirocumab: Alirocumab 25 mg administered SC	Arm G: Alirocumab Intermediate High Dose Single dose of alirocumab 50 mg SC Alirocumab: Alirocumab 50 mg administered SC	Arm H: Alirocumab High Dose Single dose of alirocumab 100 mg SC Alirocumab: Alirocumab 100 mg administered SC	Arm I: Placebo Single dose of placebo SC Placebo: Placebo administered SC
Overall Study STARTED	8	8	8	8	8	8	8	8	8
Overall Study COMPLETED	7	8	8	8	8	8	7	7	7
Overall Study NOT COMPLETED	1	0	0	0	0	0	1	1	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacodynamic Biomarkers to Support Biosimilar Development: PCSK9 Inhibitors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Evolocumab Low Dose n=8 Participants Single dose of evolocumab 21 mg subcutaneous (SC) Evolocumab: Evolocumab 21 mg administered SC	Arm B: Evolocumab Intermediate Low Dose n=8 Participants Single dose of evolocumab 35 mg SC Evolocumab: Evolocumab 35 mg administered SC	Arm C: Evolocumab Intermediate High Dose n=8 Participants Single dose of evolocumab 70 mg SC Evolocumab: Evolocumab 70 mg administered SC	Arm D: Evolocumab High Dose n=8 Participants Single dose of evolocumab 140 mg SC Evolocumab: Evolocumab 140 mg administered SC	Arm E: Alirocumab Low Dose n=8 Participants Single dose of alirocumab 15 mg SC Alirocumab: Alirocumab 15 mg administered SC	Arm F: Alirocumab Intermediate Low Dose n=8 Participants Single dose of alirocumab 25 mg SC Alirocumab: Alirocumab 25 mg administered SC	Arm G: Alirocumab Intermediate High Dose n=8 Participants Single dose of alirocumab 50 mg SC Alirocumab: Alirocumab 50 mg administered SC	Arm H: Alirocumab High Dose n=8 Participants Single dose of alirocumab 100 mg SC Alirocumab: Alirocumab 100 mg administered SC	Arm I: Placebo n=8 Participants Single dose of placebo SC Placebo: Placebo administered SC	Total n=72 Participants Total of all reporting groups
Age, Continuous	36 years n=99 Participants	37 years n=107 Participants	40 years n=206 Participants	33 years n=7 Participants	39 years n=31 Participants	31 years n=30 Participants	36 years n=3 Participants	40 years n=6 Participants	41 years n=114 Participants	36 years
Sex: Female, Male Female	3 Participants n=99 Participants	4 Participants n=107 Participants	4 Participants n=206 Participants	2 Participants n=7 Participants	3 Participants n=31 Participants	3 Participants n=30 Participants	3 Participants n=3 Participants	3 Participants n=6 Participants	3 Participants n=114 Participants	28 Participants
Sex: Female, Male Male	5 Participants n=99 Participants	4 Participants n=107 Participants	4 Participants n=206 Participants	6 Participants n=7 Participants	5 Participants n=31 Participants	5 Participants n=30 Participants	5 Participants n=3 Participants	5 Participants n=6 Participants	5 Participants n=114 Participants	44 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	4 Participants n=107 Participants	1 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 Participants	1 Participants n=30 Participants	1 Participants n=3 Participants	4 Participants n=6 Participants	3 Participants n=114 Participants	15 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=99 Participants	4 Participants n=107 Participants	7 Participants n=206 Participants	8 Participants n=7 Participants	7 Participants n=31 Participants	7 Participants n=30 Participants	7 Participants n=3 Participants	4 Participants n=6 Participants	5 Participants n=114 Participants	57 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=114 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	1 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=114 Participants	1 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=114 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	1 Participants n=114 Participants	1 Participants
Race (NIH/OMB) Black or African American	4 Participants n=99 Participants	2 Participants n=107 Participants	5 Participants n=206 Participants	2 Participants n=7 Participants	4 Participants n=31 Participants	5 Participants n=30 Participants	2 Participants n=3 Participants	2 Participants n=6 Participants	2 Participants n=114 Participants	28 Participants
Race (NIH/OMB) White	4 Participants n=99 Participants	6 Participants n=107 Participants	3 Participants n=206 Participants	6 Participants n=7 Participants	4 Participants n=31 Participants	2 Participants n=30 Participants	6 Participants n=3 Participants	5 Participants n=6 Participants	5 Participants n=114 Participants	41 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=114 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	1 Participants n=6 Participants	0 Participants n=114 Participants	1 Participants
Region of Enrollment United States	8 participants n=99 Participants	8 participants n=107 Participants	8 participants n=206 Participants	8 participants n=7 Participants	8 participants n=31 Participants	8 participants n=30 Participants	8 participants n=3 Participants	8 participants n=6 Participants	8 participants n=114 Participants	72 participants
Body weight	82 kg n=99 Participants	67 kg n=107 Participants	84 kg n=206 Participants	88 kg n=7 Participants	85 kg n=31 Participants	79 kg n=30 Participants	86 kg n=3 Participants	78 kg n=6 Participants	76 kg n=114 Participants	83 kg
Body mass index	27.7 kg/m^2 n=99 Participants	27.0 kg/m^2 n=107 Participants	28.7 kg/m^2 n=206 Participants	29.5 kg/m^2 n=7 Participants	30.1 kg/m^2 n=31 Participants	27.9 kg/m^2 n=30 Participants	28.6 kg/m^2 n=3 Participants	25.8 kg/m^2 n=6 Participants	26.8 kg/m^2 n=114 Participants	28.3 kg/m^2

PRIMARY outcome

Timeframe: Day -1 and 0h (pre-dose), 24h (post-dose); once on Day 2, 3, 4, 5, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.

Population: Analysis population includes all subjects who did not discontinue before the end of study.

Outcome measures

Outcome measures
Measure	Arm A: Evolocumab Low Dose n=7 Participants Single dose of evolocumab 21 mg subcutaneous (SC) Evolocumab: Evolocumab 21 mg administered SC	Arm B: Evolocumab Intermediate Low Dose n=8 Participants Single dose of evolocumab 35 mg SC Evolocumab: Evolocumab 35 mg administered SC	Arm C: Evolocumab Intermediate High Dose n=8 Participants Single dose of evolocumab 70 mg SC Evolocumab: Evolocumab 70 mg administered SC	Arm D: Evolocumab High Dose n=8 Participants Single dose of evolocumab 140 mg SC Evolocumab: Evolocumab 140 mg administered SC	Arm E: Alirocumab Low Dose n=8 Participants Single dose of alirocumab 15 mg SC Alirocumab: Alirocumab 15 mg administered SC	Arm F: Alirocumab Intermediate Low Dose n=8 Participants Single dose of alirocumab 25 mg SC Alirocumab: Alirocumab 25 mg administered SC	Arm G: Alirocumab Intermediate High Dose n=7 Participants Single dose of alirocumab 50 mg SC Alirocumab: Alirocumab 50 mg administered SC	Arm H: Alirocumab High Dose n=7 Participants Single dose of alirocumab 100 mg SC Alirocumab: Alirocumab 100 mg administered SC	Arm I: Placebo n=7 Participants Single dose of placebo SC Placebo: Placebo administered SC
Baseline-adjusted Area Under Effect Curve (AUEC) for LDL-C for Evolocumab and Alirocumab	-380 mg/dL*day Standard Deviation 228	-754 mg/dL*day Standard Deviation 573	-866 mg/dL*day Standard Deviation 658	-1832 mg/dL*day Standard Deviation 806	-580 mg/dL*day Standard Deviation 360	-581 mg/dL*day Standard Deviation 319	-668 mg/dL*day Standard Deviation 828	-1902 mg/dL*day Standard Deviation 361	-350 mg/dL*day Standard Deviation 881

PRIMARY outcome

Population: Analysis population includes all subjects who did not discontinue before the end of study.

The values and variability of maximum change from baseline for LDL-C at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab

Outcome measures

Outcome measures
Measure	Arm A: Evolocumab Low Dose n=7 Participants Single dose of evolocumab 21 mg subcutaneous (SC) Evolocumab: Evolocumab 21 mg administered SC	Arm B: Evolocumab Intermediate Low Dose n=8 Participants Single dose of evolocumab 35 mg SC Evolocumab: Evolocumab 35 mg administered SC	Arm C: Evolocumab Intermediate High Dose n=8 Participants Single dose of evolocumab 70 mg SC Evolocumab: Evolocumab 70 mg administered SC	Arm D: Evolocumab High Dose n=8 Participants Single dose of evolocumab 140 mg SC Evolocumab: Evolocumab 140 mg administered SC	Arm E: Alirocumab Low Dose n=8 Participants Single dose of alirocumab 15 mg SC Alirocumab: Alirocumab 15 mg administered SC	Arm F: Alirocumab Intermediate Low Dose n=8 Participants Single dose of alirocumab 25 mg SC Alirocumab: Alirocumab 25 mg administered SC	Arm G: Alirocumab Intermediate High Dose n=7 Participants Single dose of alirocumab 50 mg SC Alirocumab: Alirocumab 50 mg administered SC	Arm H: Alirocumab High Dose n=7 Participants Single dose of alirocumab 100 mg SC Alirocumab: Alirocumab 100 mg administered SC	Arm I: Placebo n=7 Participants Single dose of placebo SC Placebo: Placebo administered SC
Maximum Change From Baseline for LDL-C for Evolocumab and Alirocumab	-27.7 mg/dL Standard Deviation 11.8	-45.1 mg/dL Standard Deviation 26.9	-49.9 mg/dL Standard Deviation 26.2	-70.1 mg/dL Standard Deviation 25.0	-35.8 mg/dL Standard Deviation 16.3	-40.6 mg/dL Standard Deviation 8.1	-47.9 mg/dL Standard Deviation 18.8	-54.6 mg/dL Standard Deviation 12.1	-30.1 mg/dL Standard Deviation 18.7

SECONDARY outcome

Population: Analysis population includes all subjects who did not discontinue before the end of study.

The values and variability of AUEC for ApoB at low, intermediate-low, intermediate-high, and high doses of evolocumab and alirocumab. AUEC was calculated as the baseline-subtracted area under the ApoB concentration-time curve expressed in units of mg/(dL\*day). More negative AUEC values represent greater reductions in ApoB exposure from baseline. The standard deviation is noted in parentheses. For each subject and dose, the maximum decrease from baseline ApoB was determined using all sampled timepoints. AUEC values were log-transformed and an ANCOVA model was used to calculate geometric means and 90% confidence intervals for each treatment group.

Outcome measures

Outcome measures
Measure	Arm A: Evolocumab Low Dose n=7 Participants Single dose of evolocumab 21 mg subcutaneous (SC) Evolocumab: Evolocumab 21 mg administered SC	Arm B: Evolocumab Intermediate Low Dose n=8 Participants Single dose of evolocumab 35 mg SC Evolocumab: Evolocumab 35 mg administered SC	Arm C: Evolocumab Intermediate High Dose n=8 Participants Single dose of evolocumab 70 mg SC Evolocumab: Evolocumab 70 mg administered SC	Arm D: Evolocumab High Dose n=8 Participants Single dose of evolocumab 140 mg SC Evolocumab: Evolocumab 140 mg administered SC	Arm E: Alirocumab Low Dose n=8 Participants Single dose of alirocumab 15 mg SC Alirocumab: Alirocumab 15 mg administered SC	Arm F: Alirocumab Intermediate Low Dose n=8 Participants Single dose of alirocumab 25 mg SC Alirocumab: Alirocumab 25 mg administered SC	Arm G: Alirocumab Intermediate High Dose n=7 Participants Single dose of alirocumab 50 mg SC Alirocumab: Alirocumab 50 mg administered SC	Arm H: Alirocumab High Dose n=7 Participants Single dose of alirocumab 100 mg SC Alirocumab: Alirocumab 100 mg administered SC	Arm I: Placebo n=7 Participants Single dose of placebo SC Placebo: Placebo administered SC
Baseline-adjusted AUEC for Apolipoprotein B (ApoB) for Evolocumab and Alirocumab	-207 mg/dL*day Standard Deviation 313	-482 mg/dL*day Standard Deviation 434	-676 mg/dL*day Standard Deviation 453	-1094 mg/dL*day Standard Deviation 952	-469 mg/dL*day Standard Deviation 290	-462 mg/dL*day Standard Deviation 231	-128 mg/dL*day Standard Deviation 536	-1087 mg/dL*day Standard Deviation 707	-428 mg/dL*day Standard Deviation 560

SECONDARY outcome

Population: Analysis population includes all subjects who did not discontinue before the end of study.

The values and variability of maximal difference at a single time-point for ApoB at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab

Outcome measures

Outcome measures
Measure	Arm A: Evolocumab Low Dose n=7 Participants Single dose of evolocumab 21 mg subcutaneous (SC) Evolocumab: Evolocumab 21 mg administered SC	Arm B: Evolocumab Intermediate Low Dose n=8 Participants Single dose of evolocumab 35 mg SC Evolocumab: Evolocumab 35 mg administered SC	Arm C: Evolocumab Intermediate High Dose n=8 Participants Single dose of evolocumab 70 mg SC Evolocumab: Evolocumab 70 mg administered SC	Arm D: Evolocumab High Dose n=8 Participants Single dose of evolocumab 140 mg SC Evolocumab: Evolocumab 140 mg administered SC	Arm E: Alirocumab Low Dose n=8 Participants Single dose of alirocumab 15 mg SC Alirocumab: Alirocumab 15 mg administered SC	Arm F: Alirocumab Intermediate Low Dose n=8 Participants Single dose of alirocumab 25 mg SC Alirocumab: Alirocumab 25 mg administered SC	Arm G: Alirocumab Intermediate High Dose n=7 Participants Single dose of alirocumab 50 mg SC Alirocumab: Alirocumab 50 mg administered SC	Arm H: Alirocumab High Dose n=7 Participants Single dose of alirocumab 100 mg SC Alirocumab: Alirocumab 100 mg administered SC	Arm I: Placebo n=7 Participants Single dose of placebo SC Placebo: Placebo administered SC
Maximum Change From Baseline for apoB for Evolocumab and Alirocumab	24 mg/dL Standard Deviation 12	32 mg/dL Standard Deviation 17	36 mg/dL Standard Deviation 15	46 mg/dL Standard Deviation 16	23 mg/dL Standard Deviation 9	29 mg/dL Standard Deviation 6	28 mg/dL Standard Deviation 8	37 mg/dL Standard Deviation 7	17 mg/dL Standard Deviation 7

SECONDARY outcome

Timeframe: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8,12, 24, hours post-dose; once on Day 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 35, and 42 for all Arms. Additionally, once on Day 56 for Arms C, D, G, H, & I; and once on Day 70 and 84 for Arms D, H, & I.

Population: Analysis population includes all subjects who did not discontinue before the end of study with at least one pharmacokinetic (PK) sample above the lower limit of quantification.

The values and variability of Cmax at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab

Outcome measures

Outcome measures
Measure	Arm A: Evolocumab Low Dose n=3 Participants Single dose of evolocumab 21 mg subcutaneous (SC) Evolocumab: Evolocumab 21 mg administered SC	Arm B: Evolocumab Intermediate Low Dose n=6 Participants Single dose of evolocumab 35 mg SC Evolocumab: Evolocumab 35 mg administered SC	Arm C: Evolocumab Intermediate High Dose n=7 Participants Single dose of evolocumab 70 mg SC Evolocumab: Evolocumab 70 mg administered SC	Arm D: Evolocumab High Dose n=8 Participants Single dose of evolocumab 140 mg SC Evolocumab: Evolocumab 140 mg administered SC	Arm E: Alirocumab Low Dose n=8 Participants Single dose of alirocumab 15 mg SC Alirocumab: Alirocumab 15 mg administered SC	Arm F: Alirocumab Intermediate Low Dose n=8 Participants Single dose of alirocumab 25 mg SC Alirocumab: Alirocumab 25 mg administered SC	Arm G: Alirocumab Intermediate High Dose n=7 Participants Single dose of alirocumab 50 mg SC Alirocumab: Alirocumab 50 mg administered SC	Arm H: Alirocumab High Dose n=7 Participants Single dose of alirocumab 100 mg SC Alirocumab: Alirocumab 100 mg administered SC	Arm I: Placebo Single dose of placebo SC Placebo: Placebo administered SC
Maximum Concentration (Cmax) for Evolocumab and Alirocumab	0.7 ug/mL Geometric Coefficient of Variation 28	0.5 ug/mL Geometric Coefficient of Variation 62	2.0 ug/mL Geometric Coefficient of Variation 54	6.2 ug/mL Geometric Coefficient of Variation 36	0.8 ug/mL Geometric Coefficient of Variation 27	1.7 ug/mL Geometric Coefficient of Variation 73	2.9 ug/mL Geometric Coefficient of Variation 61	6.9 ug/mL Geometric Coefficient of Variation 41	—

SECONDARY outcome

Population: Analysis population includes all subjects who did not discontinue before the end of study with at least one PK sample above the lower limit of quantification.

The values and variability of AUC at low, intermediate low, intermediate high, and high doses of evolocumab and alirocumab

Outcome measures

Outcome measures
Measure	Arm A: Evolocumab Low Dose n=3 Participants Single dose of evolocumab 21 mg subcutaneous (SC) Evolocumab: Evolocumab 21 mg administered SC	Arm B: Evolocumab Intermediate Low Dose n=6 Participants Single dose of evolocumab 35 mg SC Evolocumab: Evolocumab 35 mg administered SC	Arm C: Evolocumab Intermediate High Dose n=7 Participants Single dose of evolocumab 70 mg SC Evolocumab: Evolocumab 70 mg administered SC	Arm D: Evolocumab High Dose n=8 Participants Single dose of evolocumab 140 mg SC Evolocumab: Evolocumab 140 mg administered SC	Arm E: Alirocumab Low Dose n=8 Participants Single dose of alirocumab 15 mg SC Alirocumab: Alirocumab 15 mg administered SC	Arm F: Alirocumab Intermediate Low Dose n=8 Participants Single dose of alirocumab 25 mg SC Alirocumab: Alirocumab 25 mg administered SC	Arm G: Alirocumab Intermediate High Dose n=7 Participants Single dose of alirocumab 50 mg SC Alirocumab: Alirocumab 50 mg administered SC	Arm H: Alirocumab High Dose n=7 Participants Single dose of alirocumab 100 mg SC Alirocumab: Alirocumab 100 mg administered SC	Arm I: Placebo Single dose of placebo SC Placebo: Placebo administered SC
Area Under the Curve (AUC) for Evolocumab and Alirocumab	2.4 mg/dL*day Geometric Coefficient of Variation 67	0.8 mg/dL*day Geometric Coefficient of Variation 91	12.9 mg/dL*day Geometric Coefficient of Variation 71	65.7 mg/dL*day Geometric Coefficient of Variation 57	8.3 mg/dL*day Geometric Coefficient of Variation 55	17.1 mg/dL*day Geometric Coefficient of Variation 57	38.5 mg/dL*day Geometric Coefficient of Variation 92	107.9 mg/dL*day Geometric Coefficient of Variation 58	—

SECONDARY outcome

Population: Analysis population for each group was limited to those subjects administered evolocumab or placebo (the evolocumab group) or administered alirocumab or placebo (alirocumab) who completed the study. Results from subjects administered placebo were used in all analyses. Confidence intervals for model parameters were generated using bootstrapping of the estimated model with 10000 repetitions.

Model parameter (slope) for LDL-C area under the effect curve model: Mean slope value calculated after combining data from low, intermediate low, intermediate high, and high doses of evolocumab or alirocumab with placebo data. The units of measure for slope are mg/dL•day / (mg dose).

Outcome measures

Outcome measures
Measure	Arm A: Evolocumab Low Dose n=38 Participants Single dose of evolocumab 21 mg subcutaneous (SC) Evolocumab: Evolocumab 21 mg administered SC	Arm B: Evolocumab Intermediate Low Dose n=37 Participants Single dose of evolocumab 35 mg SC Evolocumab: Evolocumab 35 mg administered SC	Arm C: Evolocumab Intermediate High Dose Single dose of evolocumab 70 mg SC Evolocumab: Evolocumab 70 mg administered SC	Arm D: Evolocumab High Dose Single dose of evolocumab 140 mg SC Evolocumab: Evolocumab 140 mg administered SC	Arm E: Alirocumab Low Dose Single dose of alirocumab 15 mg SC Alirocumab: Alirocumab 15 mg administered SC	Arm F: Alirocumab Intermediate Low Dose Single dose of alirocumab 25 mg SC Alirocumab: Alirocumab 25 mg administered SC	Arm G: Alirocumab Intermediate High Dose Single dose of alirocumab 50 mg SC Alirocumab: Alirocumab 50 mg administered SC	Arm H: Alirocumab High Dose Single dose of alirocumab 100 mg SC Alirocumab: Alirocumab 100 mg administered SC	Arm I: Placebo Single dose of placebo SC Placebo: Placebo administered SC
Dose-response Parameters (Slope) for LDL-C Area Under the Effect Curve Models for Evolocumab and Alirocumab	-11 mg/dL•day / (mg dose) Interval -15.0 to -6.0	-15 mg/dL•day / (mg dose) Interval -21.0 to -9.0	—	—	—	—	—	—	—

SECONDARY outcome

Model parameter (Emax) for LDL-C maximum change from baseline curve models calculated after combining data from low, intermediate low, intermediate high, and high doses of evolocumab or alirocumab with placebo data.

Outcome measures

Outcome measures
Measure	Arm A: Evolocumab Low Dose n=38 Participants Single dose of evolocumab 21 mg subcutaneous (SC) Evolocumab: Evolocumab 21 mg administered SC	Arm B: Evolocumab Intermediate Low Dose n=37 Participants Single dose of evolocumab 35 mg SC Evolocumab: Evolocumab 35 mg administered SC	Arm C: Evolocumab Intermediate High Dose Single dose of evolocumab 70 mg SC Evolocumab: Evolocumab 70 mg administered SC	Arm D: Evolocumab High Dose Single dose of evolocumab 140 mg SC Evolocumab: Evolocumab 140 mg administered SC	Arm E: Alirocumab Low Dose Single dose of alirocumab 15 mg SC Alirocumab: Alirocumab 15 mg administered SC	Arm F: Alirocumab Intermediate Low Dose Single dose of alirocumab 25 mg SC Alirocumab: Alirocumab 25 mg administered SC	Arm G: Alirocumab Intermediate High Dose Single dose of alirocumab 50 mg SC Alirocumab: Alirocumab 50 mg administered SC	Arm H: Alirocumab High Dose Single dose of alirocumab 100 mg SC Alirocumab: Alirocumab 100 mg administered SC	Arm I: Placebo Single dose of placebo SC Placebo: Placebo administered SC
Pharmacodynamic Model Parameter, Maximum Effect (Emax), for LDL-C Maximum Change From Baseline Models With Evolocumab and Alirocumab	84 mg/dL Interval 55.0 to 113.0	62 mg/dL Interval 50.0 to 75.0	—	—	—	—	—	—	—

SECONDARY outcome

Model parameter (ED50) for LDL-C maximum change from baseline curve models calculated after combining data from low, intermediate low, intermediate high, and high doses of evolocumab or alirocumab with placebo data.