Hypercholesterolemia
Conditions
Keywords
pharmacokinetics, bioavailability, PF-04950615
Brief summary
This study aims to characterize the single dose pharmacokinetics of PF-04950616 following subcutaneous injection to the abdomen, upper arm or the thigh.
Interventions
BIOLOGICALBococizumab (PF-04950615; RN316)
Single 150 mg PF-04950615 dose administered SC to the abdomen
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male and female subjects 18 to 65 years of age. * Body Mass Index (BMI) ≤ 33 kg/m2, and total body weight of 60 kg to 90 kg (132 lbs to 198 lbs). * Fasting LDL-C must be \> 130 mg/dL (borderline high per NCEP ATP III criteria) at two qualifying visits: initial screening (Days -28 to -14) and Day -7.
Exclusion criteria
* Poorly controlled type 1 or type 2 diabetes mellitus (HbA1c \> 9.0%). * History of a cardiovascular or cerebrovascular event (eg, MI, stroke, TIA) or related procedure (eg, angioplasty) during the past year. * Subjects who meet the New York Heart Association (NYHA) criteria for congestive heart failure (CHF) classes III or IV.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination. | AUCinf is the area under the plasma concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time. |
| Maximum Observed Plasma Concentration (Cmax) | Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination. | Maximum observed concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Clearance (CL/F) | Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination. | Apparent clearance following subcutaneous administration. |
| Apparent Volume of Distribution (Vz/F) | Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination. | Apparent volume of distribution following subcutaneous administration. |
| Terminal Elimination Half-Life (t1/2) | Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination. | Terminal elimination half-life following subcutaneous administration. |
| Maximum Low-density Lipoprotein Cholesterol LDL-C Lowering Effect (Emax): Absolute Value | Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination | Maximum LDL-C response using absolute on trial LDL-C data |
| Emax: Change From Baseline | Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination | LDL-C Emax expressed as change from baseline. |
| Emax: Percent Change From Baseline | Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination | LDL-C Emax expressed as percent change from baseline. |
| Time to Reach Maximum LDL-C Lowering (Tmax, LDL-C) | Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination | Time to LDL-C Emax |
| Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) | Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination. | AUClast is area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration. |
| AUEC: Change From Baseline | Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination | AUEC is the area under the LDL-C concentration-time curve from baseline to Day 85 exprssed as change from baseline |
| AUEC: Percent Change From Baseline | Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination | AUEC is the area under the LDL-C concentration-time curve from baseline to Day 85 expressed as percent change from baseline. |
| Number of Participants With Injection Site Reactions (ISRs) by Severity | Day 1 to Day 85 | Acute injection site reactions (e.g, pain, pruritus, induration) were captured as adverse events (AEs). Intensity of the AE was described as mild (does not interfere with usual function), moderate (interferes to some extent with usual function), or severe (interferes significantly with participant's usual function). |
| Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) | Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination | A participant is ADA positive if ADA titer (log2) \>=6.23. A participant is nAb positive if nAb titer (log2) \>=4.32. |
| Anti-Drug Antibody (ADA) Titer | Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination | ADA titer: titers were presented as log2 reciprocal dilution at assay cutpoint. |
| Neutralizing Antibody (nAb) Titer | Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination | nAb titer: titers were presented as log2 reciprocal dilution at assay cutpoint. |
| Area Under the LDL-C Effect Curve (AUEC): Absolute Value | Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination | AUEC is the area under the LDL-C concentration-time curve from baseline to Day 85 exprssed using absolute on trial value |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination. | Time for maximum observed concentration. |
Countries
United States
Participant flow
Pre-assignment details
Seventy-five (75) participants were enrolled and randomized in a 1:1:1 ratio to receive a single dose of Treatment A (PF-04950615 \[hereafter referred to as bococizumab\] 150 mg subcutaneously \[SC\] to the abdomen), Treatment B (bococizumab 150 mg SC to the thigh), or Treatment C (bococizumab 150 mg SC to the upper arm).
Participants by arm
| Arm | Count |
|---|---|
| Bococizumab 150 mg Abdomen Participants received a single dose of bococizumab 150 mg SC to the abdomen. | 25 |
| Bococizumab 150 mg Thigh Participants received a single dose of bococizumab 150 mg SC to the thigh. | 25 |
| Bococizumab 150 mg Upper Arm Participants received a single dose of bococizumab 150 mg SC to the upper arm. | 25 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Discontinued | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Bococizumab 150 mg Abdomen | Total | Bococizumab 150 mg Upper Arm | Bococizumab 150 mg Thigh |
|---|---|---|---|---|
| Age, Customized 18-44 years | 11 Participants | 26 Participants | 8 Participants | 7 Participants |
| Age, Customized 45-64 years | 13 Participants | 48 Participants | 17 Participants | 18 Participants |
| Age, Customized Greater than or equal to (>=) 65 years | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Age, Customized Less than (<) 18 years | 0 Participants 11.7 | 0 Participants | 0 Participants 9.6 | 0 Participants 7.5 |
| Sex: Female, Male Female | 10 Participants | 35 Participants | 13 Participants | 12 Participants |
| Sex: Female, Male Male | 15 Participants | 40 Participants | 12 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 25 | 15 / 25 | 12 / 25 |
| serious Total, serious adverse events | 0 / 25 | 1 / 25 | 0 / 25 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf)
AUCinf is the area under the plasma concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time.
Time frame: Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.
Population: The pharmacokinetic (PK) parameter analysis population included all enrolled participants who received at least 1 dose of study medication and that had at least 1 of the PK parameters of interest. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Bococizumab 150 mg Abdomen | Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | 175.9 micrograms*day/milliliter (mcg*day/mL) | Geometric Coefficient of Variation 53 |
| Bococizumab 150 mg Thigh | Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | 198.9 micrograms*day/milliliter (mcg*day/mL) | Geometric Coefficient of Variation 30 |
| Bococizumab 150 mg Upper Arm | Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | 160.3 micrograms*day/milliliter (mcg*day/mL) | Geometric Coefficient of Variation 33 |
Comparison: Thigh (Test) versus Abdomen (Reference)90% CI: [101.99, 143.45]ANCOVA
Comparison: Upper Arm (Test) versus Abdomen (Reference)90% CI: [80.2, 112.38]ANCOVA
Primary
Maximum Observed Plasma Concentration (Cmax)
Maximum observed concentration.
Time frame: Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.
Population: The PK parameter analysis population included all enrolled participants who received at least 1 dose of study medication and that had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Bococizumab 150 mg Abdomen | Maximum Observed Plasma Concentration (Cmax) | 9.68 mcg/mL | Geometric Coefficient of Variation 51 |
| Bococizumab 150 mg Thigh | Maximum Observed Plasma Concentration (Cmax) | 11.89 mcg/mL | Geometric Coefficient of Variation 30 |
| Bococizumab 150 mg Upper Arm | Maximum Observed Plasma Concentration (Cmax) | 8.14 mcg/mL | Geometric Coefficient of Variation 32 |
Comparison: Thigh (Test) versus Abdomen (Reference)90% CI: [107.19, 152.02]ANCOVA
Comparison: Upper Arm (Test) versus Abdomen (Reference)90% CI: [72.49, 102.4]ANCOVA
Secondary
Anti-Drug Antibody (ADA) Titer
ADA titer: titers were presented as log2 reciprocal dilution at assay cutpoint.
Time frame: Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination
Population: The safety analysis population included all participants who received at least 1 dose of study medication. Only confirmed ADA positive samples were analyzed for titer.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Bococizumab 150 mg Abdomen | Anti-Drug Antibody (ADA) Titer | Day 15 | NA Log2 titer |
| Bococizumab 150 mg Abdomen | Anti-Drug Antibody (ADA) Titer | Day 85 | 7.46 Log2 titer |
| Bococizumab 150 mg Abdomen | Anti-Drug Antibody (ADA) Titer | Day 29 | NA Log2 titer |
| Bococizumab 150 mg Abdomen | Anti-Drug Antibody (ADA) Titer | Day 57 | NA Log2 titer |
| Bococizumab 150 mg Thigh | Anti-Drug Antibody (ADA) Titer | Day 57 | 7.64 Log2 titer |
| Bococizumab 150 mg Thigh | Anti-Drug Antibody (ADA) Titer | Day 29 | NA Log2 titer |
| Bococizumab 150 mg Thigh | Anti-Drug Antibody (ADA) Titer | Day 15 | NA Log2 titer |
| Bococizumab 150 mg Thigh | Anti-Drug Antibody (ADA) Titer | Day 85 | 7.20 Log2 titer |
| Bococizumab 150 mg Upper Arm | Anti-Drug Antibody (ADA) Titer | Day 85 | 7.60 Log2 titer |
| Bococizumab 150 mg Upper Arm | Anti-Drug Antibody (ADA) Titer | Day 57 | 8.25 Log2 titer |
Secondary
Apparent Clearance (CL/F)
Apparent clearance following subcutaneous administration.
Time frame: Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.
Population: The PK parameter analysis population included all enrolled participants who received at least 1 dose of study medication and that had at least 1 of the PK parameters of interest. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Bococizumab 150 mg Abdomen | Apparent Clearance (CL/F) | 0.8521 liters per day | Geometric Coefficient of Variation 53 |
| Bococizumab 150 mg Thigh | Apparent Clearance (CL/F) | 0.7545 liters per day | Geometric Coefficient of Variation 30 |
| Bococizumab 150 mg Upper Arm | Apparent Clearance (CL/F) | 0.9352 liters per day | Geometric Coefficient of Variation 33 |
Secondary
Apparent Volume of Distribution (Vz/F)
Apparent volume of distribution following subcutaneous administration.
Time frame: Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.
Population: The PK parameter analysis population included all enrolled participants who received at least 1 dose of study medication and that had at least 1 of the PK parameters of interest. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Bococizumab 150 mg Abdomen | Apparent Volume of Distribution (Vz/F) | 8.84 liters | Geometric Coefficient of Variation 49 |
| Bococizumab 150 mg Thigh | Apparent Volume of Distribution (Vz/F) | 7.98 liters | Geometric Coefficient of Variation 29 |
| Bococizumab 150 mg Upper Arm | Apparent Volume of Distribution (Vz/F) | 11.33 liters | Geometric Coefficient of Variation 36 |
Secondary
Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast)
AUClast is area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration.
Time frame: Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.
Population: The PK parameter analysis population included all enrolled participants who received at least 1 dose of study medication and that had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Bococizumab 150 mg Abdomen | Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) | 158.8 mcg*day/mL | Geometric Coefficient of Variation 65 |
| Bococizumab 150 mg Thigh | Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) | 192.5 mcg*day/mL | Geometric Coefficient of Variation 31 |
| Bococizumab 150 mg Upper Arm | Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) | 152.6 mcg*day/mL | Geometric Coefficient of Variation 36 |
Comparison: Thigh (Test) versus Abdomen (Reference)90% CI: [106.76, 158.27]ANCOVA
Comparison: Upper Arm (Test) versus Abdomen (Reference)90% CI: [82.54, 121.82]ANCOVA
Secondary
Area Under the LDL-C Effect Curve (AUEC): Absolute Value
AUEC is the area under the LDL-C concentration-time curve from baseline to Day 85 exprssed using absolute on trial value
Time frame: Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination
Population: The PD analysis population included all enrolled participants who received at least 1 dose of study medication and had both baseline and post-baseline values for at least 1 of the PD endpoints. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bococizumab 150 mg Abdomen | Area Under the LDL-C Effect Curve (AUEC): Absolute Value | 11181.64 mg*day/dL | Standard Deviation 1545.335 |
| Bococizumab 150 mg Thigh | Area Under the LDL-C Effect Curve (AUEC): Absolute Value | 11682.39 mg*day/dL | Standard Deviation 2063.772 |
| Bococizumab 150 mg Upper Arm | Area Under the LDL-C Effect Curve (AUEC): Absolute Value | 11231.39 mg*day/dL | Standard Deviation 1928.904 |
90% CI: [97.555, 107.717]ANCOVA
90% CI: [97.131, 107.151]ANCOVA
Secondary
AUEC: Change From Baseline
AUEC is the area under the LDL-C concentration-time curve from baseline to Day 85 exprssed as change from baseline
Time frame: Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination
Population: The PD analysis population included all enrolled participants who received at least 1 dose of study medication and had both baseline and post-baseline values for at least 1 of the PD endpoints. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bococizumab 150 mg Abdomen | AUEC: Change From Baseline | -2982.16 mg*day/dL | Standard Deviation 1431.589 |
| Bococizumab 150 mg Thigh | AUEC: Change From Baseline | -2701.99 mg*day/dL | Standard Deviation 1432.539 |
| Bococizumab 150 mg Upper Arm | AUEC: Change From Baseline | -2546.68 mg*day/dL | Standard Deviation 977.934 |
90% CI: [60.883, 102.735]ANCOVA
90% CI: [70.269, 118.248]ANCOVA
Secondary
AUEC: Percent Change From Baseline
AUEC is the area under the LDL-C concentration-time curve from baseline to Day 85 expressed as percent change from baseline.
Time frame: Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination
Population: The PD analysis population included all enrolled participants who received at least 1 dose of study medication and had both baseline and post-baseline values for at least 1 of the PD endpoints. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bococizumab 150 mg Abdomen | AUEC: Percent Change From Baseline | -1715.22 percent change | Standard Deviation 758.72 |
| Bococizumab 150 mg Thigh | AUEC: Percent Change From Baseline | -1538.85 percent change | Standard Deviation 724.925 |
| Bococizumab 150 mg Upper Arm | AUEC: Percent Change From Baseline | -1550.73 percent change | Standard Deviation 583.745 |
90% CI: [60.883, 102.735]ANCOVA
90% CI: [70.269, 118.248]ANCOVA
Secondary
Emax: Change From Baseline
LDL-C Emax expressed as change from baseline.
Time frame: Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination
Population: The PD analysis population included all enrolled participants who received at least 1 dose of study medication and had both baseline and post-baseline values for at least 1 of the PD endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bococizumab 150 mg Abdomen | Emax: Change From Baseline | -96.88 mg/dL | Standard Deviation 19.356 |
| Bococizumab 150 mg Thigh | Emax: Change From Baseline | -97.62 mg/dL | Standard Deviation 26.967 |
| Bococizumab 150 mg Upper Arm | Emax: Change From Baseline | -90.46 mg/dL | Standard Deviation 25.441 |
90% CI: [86.558, 108.926]ANCOVA
90% CI: [83.359, 104.912]ANCOVA
Secondary
Emax: Percent Change From Baseline
LDL-C Emax expressed as percent change from baseline.
Time frame: Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination
Population: The PD analysis population included all enrolled participants who received at least 1 dose of study medication and had both baseline and post-baseline values for at least 1 of the PD endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bococizumab 150 mg Abdomen | Emax: Percent Change From Baseline | -57.47 percent change | Standard Deviation 9.084 |
| Bococizumab 150 mg Thigh | Emax: Percent Change From Baseline | -56.98 percent change | Standard Deviation 14.74 |
| Bococizumab 150 mg Upper Arm | Emax: Percent Change From Baseline | -54.96 percent change | Standard Deviation 13.269 |
90% CI: [86.558, 108.926]ANCOVA
90% CI: [83.359, 104.912]ANCOVA
Secondary
Maximum Low-density Lipoprotein Cholesterol LDL-C Lowering Effect (Emax): Absolute Value
Maximum LDL-C response using absolute on trial LDL-C data
Time frame: Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination
Population: The pharmacodynamic (PD) analysis population included all enrolled participants who received at least 1 dose of study medication and had both baseline and post-baseline values for at least 1 of the PD endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bococizumab 150 mg Abdomen | Maximum Low-density Lipoprotein Cholesterol LDL-C Lowering Effect (Emax): Absolute Value | 72.20 mg/dL | Standard Deviation 20.185 |
| Bococizumab 150 mg Thigh | Maximum Low-density Lipoprotein Cholesterol LDL-C Lowering Effect (Emax): Absolute Value | 75.32 mg/dL | Standard Deviation 31.964 |
| Bococizumab 150 mg Upper Arm | Maximum Low-density Lipoprotein Cholesterol LDL-C Lowering Effect (Emax): Absolute Value | 74.40 mg/dL | Standard Deviation 25.29 |
90% CI: [84.659, 111.943]ANCOVA
90% CI: [90.405, 119.557]ANCOVA
Secondary
Neutralizing Antibody (nAb) Titer
nAb titer: titers were presented as log2 reciprocal dilution at assay cutpoint.
Time frame: Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination
Population: The safety analysis population included all participants who received at least 1 dose of study medication. Only confirmed ADA positive samples were analyzed for nAb. nAb titer was determined if a sample is screened positive for nAb. nAb titer data for the Bococizumab 150 mg Upper Arm group is not presented as there were no nAb positive subjects.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Bococizumab 150 mg Abdomen | Neutralizing Antibody (nAb) Titer | Day 29 | NA Log2 titer |
| Bococizumab 150 mg Abdomen | Neutralizing Antibody (nAb) Titer | Day 57 | NA Log2 titer |
| Bococizumab 150 mg Abdomen | Neutralizing Antibody (nAb) Titer | Day 85 | NA Log2 titer |
| Bococizumab 150 mg Thigh | Neutralizing Antibody (nAb) Titer | Day 85 | NA Log2 titer |
| Bococizumab 150 mg Thigh | Neutralizing Antibody (nAb) Titer | Day 57 | NA Log2 titer |
Secondary
Number of Participants With Injection Site Reactions (ISRs) by Severity
Acute injection site reactions (e.g, pain, pruritus, induration) were captured as adverse events (AEs). Intensity of the AE was described as mild (does not interfere with usual function), moderate (interferes to some extent with usual function), or severe (interferes significantly with participant's usual function).
Time frame: Day 1 to Day 85
Population: The safety analysis population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site erythema | 0 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site reaction | 1 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site indurations | 0 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site pain | 0 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site indurations | 1 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site pruritus | 0 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site swelling | 0 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site reaction | 0 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site swelling | 0 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site erythema | 0 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site indurations | 0 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site pain | 1 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site pain | 0 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site pruritus | 0 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site erythema | 1 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site reaction | 0 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site pruritus | 0 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site swelling | 0 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site reaction | 0 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site erythema | 0 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site erythema | 0 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site erythema | 0 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site indurations | 0 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site reaction | 3 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site pruritus | 0 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site pain | 0 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site indurations | 0 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site swelling | 0 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site pruritus | 0 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site pruritus | 0 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site pain | 0 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site reaction | 0 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site swelling | 1 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site pain | 0 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site swelling | 0 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site indurations | 2 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site swelling | 0 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site erythema | 2 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site indurations | 0 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site pain | 0 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site reaction | 1 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site swelling | 0 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site erythema | 0 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site indurations | 0 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site pain | 0 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site pruritus | 0 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site reaction | 0 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Moderate: injection site swelling | 0 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site erythema | 0 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site indurations | 0 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site pain | 0 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site pruritus | 0 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Severe: injection site reaction | 0 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Injection Site Reactions (ISRs) by Severity | Mild: injection site pruritus | 1 participants |
Secondary
Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb)
A participant is ADA positive if ADA titer (log2) \>=6.23. A participant is nAb positive if nAb titer (log2) \>=4.32.
Time frame: Day 1, Day 15, Day 29, Day 57 and Day 85/Early Termination
Population: The safety analysis population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bococizumab 150 mg Abdomen | Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) | Positive ADA | 6 participants |
| Bococizumab 150 mg Abdomen | Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) | Positive nAb | 2 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) | Positive ADA | 6 participants |
| Bococizumab 150 mg Thigh | Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) | Positive nAb | 2 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) | Positive ADA | 11 participants |
| Bococizumab 150 mg Upper Arm | Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) | Positive nAb | 0 participants |
Secondary
Terminal Elimination Half-Life (t1/2)
Terminal elimination half-life following subcutaneous administration.
Time frame: Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.
Population: The PK parameter analysis population included all enrolled participants who received at least 1 dose of study medication and that had at least 1 of the PK parameters of interest. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bococizumab 150 mg Abdomen | Terminal Elimination Half-Life (t1/2) | 7.27 days | Standard Deviation 1.09 |
| Bococizumab 150 mg Thigh | Terminal Elimination Half-Life (t1/2) | 7.40 days | Standard Deviation 1.03 |
| Bococizumab 150 mg Upper Arm | Terminal Elimination Half-Life (t1/2) | 8.53 days | Standard Deviation 1.61 |
Secondary
Time to Reach Maximum LDL-C Lowering (Tmax, LDL-C)
Time to LDL-C Emax
Time frame: Baseline (average of Day -7 and Day 1), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination
Population: The PD analysis population included all enrolled participants who received at least 1 dose of study medication and had both baseline and post-baseline values for at least 1 of the PD endpoints.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Bococizumab 150 mg Abdomen | Time to Reach Maximum LDL-C Lowering (Tmax, LDL-C) | 20.96 days | Full Range 7.461 |
| Bococizumab 150 mg Thigh | Time to Reach Maximum LDL-C Lowering (Tmax, LDL-C) | 20.06 days | Full Range 5.173 |
| Bococizumab 150 mg Upper Arm | Time to Reach Maximum LDL-C Lowering (Tmax, LDL-C) | 14.01 days | Full Range 7.102 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time for maximum observed concentration.
Time frame: Day 1 (Hour 0 pre-dose, Hours 1 and 8 post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71 and Day 85/Early Termination.
Population: The PK parameter analysis population included all enrolled participants who received at least 1 dose of study medication and that had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bococizumab 150 mg Abdomen | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 5.04 days |
| Bococizumab 150 mg Thigh | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 4.25 days |
| Bococizumab 150 mg Upper Arm | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 6.93 days |