Hyperlipidemia
Conditions
Keywords
mixed dyslipidemia
Brief summary
This study is a multicenter, randomized study in subjects with high cholesterol receiving statins to assess the efficacy to lower LDL-C, the safety, tolerability and actual use of bococizumab and an autoinjector (pre-filled pen).
Interventions
BIOLOGICALBococizumab 150mg
Bococizumab autoinjector (pre-filled pen) combination Product. 150mg every 2 weeks for 10 weeks, subcutaneous injection.
BIOLOGICALBococizumab 75mg
Bococizumab autoinjector (pre-filled pen) combination Product. 75mg every 2 weeks for 10 weeks, subcutaneous injection.
BIOLOGICALBococizumab 150mg placebo
Bococizumab placebo autoinjector (pre-filled pen) combination Product. 150mg placebo every 2 weeks for 10 weeks, subcutaneous injection.
BIOLOGICALBococizumab 75mg placebo
Bococizumab placebo autoinjector (pre-filled pen) combination product. 75mg placebo every 2 weeks for 10 weeks, subcutaneous injection.
Sponsors
Pfizer
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Treated with a statin - Fasting LDL-C \>=70mg/dL and triglycerides \<=400mg/dL
Exclusion criteria
* Pregnant or breastfeeding females - Cardiovascular or cerebrovascular event or procedures during the past 90 days - Congestive heart failure NYHA class IV - Poorly controlled hypertension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline at Week 12 in Fasting Low Density Lipoprotein Cholesterol (LDL-C) Level for Bococizumab 150 mg Dose Group and Matched Placebo | Baseline, Week 12 | — |
| Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 0 (Day 1) | Week 0 (Day 1) | A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn? |
| Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 2 | Week 2 | A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn? |
| Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 4 | Week 4 | A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn? |
| Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 6 | Week 6 | A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn? |
| Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 8 | Week 8 | A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn? |
| Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 10 | Week 10 | A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn? |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) | Baseline up to 18 weeks | Percentage of participants with at least 1 positive ADA titer or 1 positive nAb titer were reported. Participants with their ADA titer levels \>=6.23 were considered as ADA positive and participants with their nAb titer level \>=1.58 were considered as nAb positive. |
| Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 2, 4, 6, 8 and 10 | Week 0 (Day 1), 2, 4, 6, 8, 10 | A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn? |
| Plasma Concentration of Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) at Week 12 | Week 12 | PCSK9 is an enzyme encoded by the PCSK9 gene in humans on chromosome. It is the 9th member of the proprotein convertase family of proteins that activate other proteins. |
| Plasma Concentration of Bococizumab at Week 12 | Week 12 | — |
| Percentage of Injections That Met the Definition for Successful Assessment Using the Observer Assessment Tool (OAT) for Bococizumab 150 mg Dose, Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 4 and 8 | Week 0 (Day 1), 4, 8 | As per the OAT, a 'successful' injection was based on observer's response for the question - Was the administration successful?''. Observer's response being 'Yes' corresponded to a successful injection. |
| Percent Change From Baseline at Week 12 in Fasting Low Density Lipoprotein Cholesterol (LDL-C) Level for Bococizumab 75 mg Dose Group and Matched Placebo | Baseline, Week 12 | — |
| Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 | Baseline, Week 12 | — |
| Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 12 | Baseline, Week 12 | — |
| Percent Change From Baseline in Fasting Non- High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12 | Baseline, Week 12 | — |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to 18 weeks | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug up to the follow up visit (up to 18 weeks), that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matched to Bococizumab 150 mg Participants received single dose of placebo matched to bococizumab 150 milligram (mg) subcutaneous injection once in every 2 weeks over a period of 12 weeks. Participants were followed up to 18 weeks. | 50 |
| Bococizumab 150 mg Participants received single dose of bococizumab 150 mg subcutaneous injection once in every 2 weeks, over a period of 12 weeks. Participants were followed up to 18 weeks. | 100 |
| Placebo Matched to Bococizumab 75 mg Participants received single dose of placebo matched to bococizumab 75 mg subcutaneous injection once in every 2 weeks, over a period of 12 weeks. Participants were followed up to 18 weeks. | 49 |
| Bococizumab 75 mg Participants received single dose of bococizumab 75 mg subcutaneous injection once in every 2 weeks, over a period of 12 weeks. Participants were followed up to 18 weeks. | 100 |
| Total | 299 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 |
| Overall Study | Relocated Out of State | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo Matched to Bococizumab 150 mg | Bococizumab 150 mg | Placebo Matched to Bococizumab 75 mg | Bococizumab 75 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 61.5 years STANDARD_DEVIATION 12 | 58.9 years STANDARD_DEVIATION 11.5 | 61 years STANDARD_DEVIATION 9.7 | 59.9 years STANDARD_DEVIATION 10.1 | 60 years STANDARD_DEVIATION 10.9 |
| Sex: Female, Male Female | 18 Participants | 42 Participants | 29 Participants | 48 Participants | 137 Participants |
| Sex: Female, Male Male | 32 Participants | 58 Participants | 20 Participants | 52 Participants | 162 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 50 | 6 / 100 | 6 / 49 | 5 / 100 |
| serious Total, serious adverse events | 0 / 50 | 2 / 100 | 3 / 49 | 2 / 100 |
Outcome results
Primary
Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 0 (Day 1)
A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn?
Time frame: Week 0 (Day 1)
Population: Full analysis set included all participants who were randomized. Data for this outcome measure was not planned to be analyzed for placebo arms, as pre-specified in protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matched to Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 0 (Day 1) | 98 percentage of injections |
Primary
Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 10
A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn?
Time frame: Week 10
Population: Full analysis set included all participants who were randomized. Data for this outcome measure was not planned to be analyzed for placebo arms, as pre-specified in protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matched to Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 10 | 98.0 percentage of injections |
Primary
Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 2
A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn?
Time frame: Week 2
Population: Full analysis set included all participants who were randomized. Data for this outcome measure was not planned to be analyzed for placebo arms, as pre-specified in protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matched to Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 2 | 94.2 percentage of injections |
Primary
Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 4
A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn?
Time frame: Week 4
Population: Full analysis set included all participants who were randomized. Data for this outcome measure was not planned to be analyzed for placebo arms, as pre-specified in protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matched to Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 4 | 93.3 percentage of injections |
Primary
Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 6
A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn?
Time frame: Week 6
Population: Full analysis set included all participants who were randomized. Data for this outcome measure was not planned to be analyzed for placebo arms, as pre-specified in protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matched to Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 6 | 96 percentage of injections |
Primary
Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 8
A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn?
Time frame: Week 8
Population: Full analysis set included all participants who were randomized. Data for this outcome measure was not planned to be analyzed for placebo arms, as pre-specified in protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matched to Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 150 mg Dose Group at Week 8 | 99 percentage of injections |
Primary
Percent Change From Baseline at Week 12 in Fasting Low Density Lipoprotein Cholesterol (LDL-C) Level for Bococizumab 150 mg Dose Group and Matched Placebo
Time frame: Baseline, Week 12
Population: Full analysis set included all participants who were randomized. Here, 'number of participants analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matched to Bococizumab 150 mg | Percent Change From Baseline at Week 12 in Fasting Low Density Lipoprotein Cholesterol (LDL-C) Level for Bococizumab 150 mg Dose Group and Matched Placebo | 6.2 percent change | Standard Error 3.57 |
| Bococizumab 150 mg | Percent Change From Baseline at Week 12 in Fasting Low Density Lipoprotein Cholesterol (LDL-C) Level for Bococizumab 150 mg Dose Group and Matched Placebo | -57.2 percent change | Standard Error 2.57 |
Comparison: LS-mean difference, associated 95% confidence intervals, and p-value are from MMRM model with fixed effects for treatment groups, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction as covariates.p-value: <0.00195% CI: [-72, -54.7]Mixed Models Repeated Measures (MMRM)
Secondary
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug up to the follow up visit (up to 18 weeks), that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.
Time frame: Baseline up to 18 weeks
Population: Safety analysis set included all participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Matched to Bococizumab 150 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| Placebo Matched to Bococizumab 150 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 17 participants |
| Bococizumab 150 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 42 participants |
| Bococizumab 150 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 2 participants |
| Bococizumab 150 + Bococizumab 75 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 20 participants |
| Bococizumab 150 + Bococizumab 75 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 3 participants |
| Bococizumab 75 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 2 participants |
| Bococizumab 75 mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 33 participants |
Secondary
Percentage of Injections That Met the Definition for Successful Assessment Using the Observer Assessment Tool (OAT) for Bococizumab 150 mg Dose, Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 4 and 8
As per the OAT, a 'successful' injection was based on observer's response for the question - Was the administration successful?''. Observer's response being 'Yes' corresponded to a successful injection.
Time frame: Week 0 (Day 1), 4, 8
Population: Full analysis set included all participants who were randomized. Data for this outcome measure was not planned to be analyzed for placebo arms as pre-specified in protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Matched to Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Observer Assessment Tool (OAT) for Bococizumab 150 mg Dose, Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 4 and 8 | Week 4 | 93.2 percentage of injections |
| Placebo Matched to Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Observer Assessment Tool (OAT) for Bococizumab 150 mg Dose, Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 4 and 8 | Week 0 | 99.0 percentage of injections |
| Placebo Matched to Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Observer Assessment Tool (OAT) for Bococizumab 150 mg Dose, Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 4 and 8 | Week 8 | 100.0 percentage of injections |
| Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Observer Assessment Tool (OAT) for Bococizumab 150 mg Dose, Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 4 and 8 | Week 4 | 99.0 percentage of injections |
| Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Observer Assessment Tool (OAT) for Bococizumab 150 mg Dose, Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 4 and 8 | Week 0 | 98.0 percentage of injections |
| Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Observer Assessment Tool (OAT) for Bococizumab 150 mg Dose, Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 4 and 8 | Week 8 | 100.0 percentage of injections |
| Bococizumab 150 + Bococizumab 75 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Observer Assessment Tool (OAT) for Bococizumab 150 mg Dose, Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 4 and 8 | Week 0 | 98.5 percentage of injections |
| Bococizumab 150 + Bococizumab 75 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Observer Assessment Tool (OAT) for Bococizumab 150 mg Dose, Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 4 and 8 | Week 8 | 100.0 percentage of injections |
| Bococizumab 150 + Bococizumab 75 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Observer Assessment Tool (OAT) for Bococizumab 150 mg Dose, Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 4 and 8 | Week 4 | 96.1 percentage of injections |
Secondary
Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 2, 4, 6, 8 and 10
A successful injection based on PAT was an injection where the participant answered yes to all the three questions: Were you able to inject your medicine? Has the blue bar moved across the window? Was the medicine not flowing after needle withdrawn?
Time frame: Week 0 (Day 1), 2, 4, 6, 8, 10
Population: Full analysis set included all participants who were randomized. Data for this outcome measure was not planned to be analyzed for placebo arms, as pre-specified in protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Matched to Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 2, 4, 6, 8 and 10 | Week 0 | 97.0 percentage of injections |
| Placebo Matched to Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 2, 4, 6, 8 and 10 | Week 2 | 94.1 percentage of injections |
| Placebo Matched to Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 2, 4, 6, 8 and 10 | Week 4 | 99.0 percentage of injections |
| Placebo Matched to Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 2, 4, 6, 8 and 10 | Week 6 | 97.0 percentage of injections |
| Placebo Matched to Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 2, 4, 6, 8 and 10 | Week 8 | 100.0 percentage of injections |
| Placebo Matched to Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 2, 4, 6, 8 and 10 | Week 10 | 97.0 percentage of injections |
| Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 2, 4, 6, 8 and 10 | Week 8 | 99.5 percentage of injections |
| Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 2, 4, 6, 8 and 10 | Week 0 | 97.5 percentage of injections |
| Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 2, 4, 6, 8 and 10 | Week 6 | 96.5 percentage of injections |
| Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 2, 4, 6, 8 and 10 | Week 2 | 94.1 percentage of injections |
| Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 2, 4, 6, 8 and 10 | Week 10 | 97.5 percentage of injections |
| Bococizumab 150 mg | Percentage of Injections That Met the Definition for Successful Assessment Using the Participant Assessment Tool (PAT) for Bococizumab 75 mg Dose Group and Combined Bococizumab 150 mg and 75 mg Dose Group at Week 0 (Day 1), 2, 4, 6, 8 and 10 | Week 4 | 96.1 percentage of injections |
Secondary
Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb)
Percentage of participants with at least 1 positive ADA titer or 1 positive nAb titer were reported. Participants with their ADA titer levels \>=6.23 were considered as ADA positive and participants with their nAb titer level \>=1.58 were considered as nAb positive.
Time frame: Baseline up to 18 weeks
Population: Safety analysis set included all participants who received at least 1 dose of study treatment. Participants who received at least 1 dose of bococizumab were evaluable for this outcome measure. Here, 'number of participants analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Matched to Bococizumab 150 mg | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) | ADA Positive | 39.2 percentage of participants |
| Placebo Matched to Bococizumab 150 mg | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) | nAb Positive | 18.6 percentage of participants |
| Bococizumab 150 mg | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) | ADA Positive | 22.2 percentage of participants |
| Bococizumab 150 mg | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb) | nAb Positive | 11.1 percentage of participants |
Secondary
Percent Change From Baseline at Week 12 in Fasting Low Density Lipoprotein Cholesterol (LDL-C) Level for Bococizumab 75 mg Dose Group and Matched Placebo
Time frame: Baseline, Week 12
Population: Full analysis set included all participants who were randomized. Here, 'number of participants analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matched to Bococizumab 150 mg | Percent Change From Baseline at Week 12 in Fasting Low Density Lipoprotein Cholesterol (LDL-C) Level for Bococizumab 75 mg Dose Group and Matched Placebo | 6.9 percent change | Standard Error 3.74 |
| Bococizumab 150 mg | Percent Change From Baseline at Week 12 in Fasting Low Density Lipoprotein Cholesterol (LDL-C) Level for Bococizumab 75 mg Dose Group and Matched Placebo | -36.0 percent change | Standard Error 2.55 |
Comparison: LS-mean differences and associated 95% confidence intervals, and p-values are from an MMRM model with fixed effects for treatment groups, visit, treatment group \* visit interaction, baseline value, baseline value \* visit interaction as covariates.p-value: <0.00195% CI: [-51.9, -34]MMRM
Secondary
Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 12
Time frame: Baseline, Week 12
Population: Full analysis set included all participants who were randomized. Here, 'number of participants analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matched to Bococizumab 150 mg | Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 12 | 4.5 percent change | Standard Error 3.44 |
| Bococizumab 150 mg | Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 12 | -53.4 percent change | Standard Error 2.48 |
| Bococizumab 150 + Bococizumab 75 mg | Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 12 | 4.3 percent change | Standard Error 3.62 |
| Bococizumab 75 mg | Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 12 | -31.5 percent change | Standard Error 2.46 |
Comparison: LS-mean differences and associated 95% confidence intervals, and p-values are from an MMRM model with fixed effects for treatment groups, visit, treatment group \* visit interaction, baseline value, baseline value \* visit interaction as covariates.p-value: <0.00195% CI: [-66.2, -49.5]MMRM
Comparison: LS-mean differences and associated 95% confidence intervals, and p-values are from an MMRM model with fixed effects for treatment groups, visit, treatment group \* visit interaction, baseline value, baseline value \* visit interaction as covariates.p-value: <0.00195% CI: [-44.4, -27.1]MMRM
Secondary
Percent Change From Baseline in Fasting Non- High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12
Time frame: Baseline, Week 12
Population: Full analysis set included all participants who were randomized. Here, 'number of participants analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matched to Bococizumab 150 mg | Percent Change From Baseline in Fasting Non- High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12 | 4.1 percent change | Standard Error 3.12 |
| Bococizumab 150 mg | Percent Change From Baseline in Fasting Non- High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12 | -52.1 percent change | Standard Error 2.24 |
| Bococizumab 150 + Bococizumab 75 mg | Percent Change From Baseline in Fasting Non- High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12 | 4.7 percent change | Standard Error 3.3 |
| Bococizumab 75 mg | Percent Change From Baseline in Fasting Non- High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12 | -32.5 percent change | Standard Error 2.23 |
Comparison: LS-mean differences and associated 95% confidence intervals, and p-values are from an MMRM model with fixed effects for treatment groups, visit, treatment group \* visit interaction, baseline value, baseline value \* visit interaction as covariates.p-value: <0.00195% CI: [-63.7, -48.6]MMRM
Comparison: LS-mean differences and associated 95% confidence intervals, and p-values are from an MMRM model with fixed effects for treatment groups, visit, treatment group \* visit interaction, baseline value, baseline value \* visit interaction as covariates.p-value: <0.00195% CI: [-45, -29.3]MMRM
Secondary
Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12
Time frame: Baseline, Week 12
Population: Full analysis set included all participants who were randomized. Here, 'number of participants analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matched to Bococizumab 150 mg | Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 | 3.8 percent change | Standard Error 2.33 |
| Bococizumab 150 mg | Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 | -35.9 percent change | Standard Error 1.67 |
| Bococizumab 150 + Bococizumab 75 mg | Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 | 4.7 percent change | Standard Error 2.45 |
| Bococizumab 75 mg | Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 | -22.0 percent change | Standard Error 1.66 |
Comparison: LS-mean differences and associated 95% confidence intervals, and p-values are from an MMRM model with fixed effects for treatment groups, visit, treatment group \* visit interaction, baseline value, baseline value \* visit interaction as covariates.p-value: <0.00195% CI: [-45.4, -34.1]MMRM
Comparison: LS-mean differences and associated 95% confidence intervals, and p-values are from an MMRM model with fixed effects for treatment groups, visit, treatment group \* visit interaction, baseline value, baseline value \* visit interaction as covariates.p-value: <0.00195% CI: [-32.5, -20.8]MMRM
Secondary
Plasma Concentration of Bococizumab at Week 12
Time frame: Week 12
Population: Analysis set included all participants who received at least one dose of study medication. Participants who received at least 1 dose of Bococizumab were evaluable for this outcome measure. Here, 'number of participants analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matched to Bococizumab 150 mg | Plasma Concentration of Bococizumab at Week 12 | 6.68 microgram per milliliter | Standard Deviation 6.169 |
| Bococizumab 150 mg | Plasma Concentration of Bococizumab at Week 12 | 2.08 microgram per milliliter | Standard Deviation 1.413 |
Secondary
Plasma Concentration of Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) at Week 12
PCSK9 is an enzyme encoded by the PCSK9 gene in humans on chromosome. It is the 9th member of the proprotein convertase family of proteins that activate other proteins.
Time frame: Week 12
Population: Safety analysis set included all participants who received at least 1 dose of study treatment. Here, 'number of participants analyzed' signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Matched to Bococizumab 150 mg | Plasma Concentration of Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) at Week 12 | 297.9 nanogram per milliliter | Standard Deviation 102.11 |
| Bococizumab 150 mg | Plasma Concentration of Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) at Week 12 | 2835.3 nanogram per milliliter | Standard Deviation 901.15 |
| Bococizumab 150 + Bococizumab 75 mg | Plasma Concentration of Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) at Week 12 | 341.8 nanogram per milliliter | Standard Deviation 102.91 |
| Bococizumab 75 mg | Plasma Concentration of Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) at Week 12 | 2370.9 nanogram per milliliter | Standard Deviation 1016.4 |