Cardiovascular Disease
Conditions
Keywords
myocardial infarction, stroke, hyperlipidemia
Brief summary
This study evaluates the PCSK9 inhibitor, Bococizumab (PF-04950615;RN316), compared to placebo, in reducing the occurrrence of major cardiovascular events, including cardiovascular death, myocardial infarction, stroke, and unstable angina requiring urgent revascularization in high risk subjects who are receiving background lipid lowering therapy and have cholesterol laboratory values of LDL-C \>/= 100 mg/dL (2.6 mmol/L) or non-HDL-C \>/=130 mg/dL (3.4 mmol/L).
Detailed description
The trial was terminated prematurely on November 1, 2016, due to the emerging clinical profile and the evolving treatment and market landscape for lipid-lowering agents. These indicated that bococizumab was not likely to provide value to patients, physicians, or shareholders. The decision was not based on a recommendation by the independent Data Monitoring Committee to stop the program.
Interventions
150 mg, every 2 weeks, subcutaneous. The duration of the treatment period will depend upon reaching the targeted number of adjudicated and confirmed CV outcome events, approximately 3 to 4 years after the entry of first subject into the study.
DRUGPlacebo
Placebo comparator, every 2 weeks, subcutaneous. The duration of the treatment period will depend upon reaching the targeted number of adjudicated and confirmed CV outcome events, approximately 3 to 4 years after the entry of first subject into the study.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be on background lipid lowering treatment. * Must be at high risk of a CV event. * Must have an LDL C \>/=100 mg/dL (2.6 mmol/L) OR non HDL C \>/=130 mg/dL (3.4 mmol/L).
Exclusion criteria
* Planned coronary (PCI or CABG) or other arterial revascularization. * New York Heart Association Class IV congestive heart failure or left ventricular ejection fraction \< 25% by cardiac imaging. * Chronic renal insufficiency with creatinine clearance of \<30 ml/min/1.73m\^2 by MDRD formula or with end state renal disease on dialysis. * History of hemorrhagic stroke. * Prior exposure to bococizumab or other investigational PCSK9 inhibitor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event Rate Per 100 Participant-years for First Occurrence of Major Cardiovascular (CV) Event | From baseline until the date of first adjudicated and confirmed occurrence of major CV event (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for first occurrence of major CV event (adjudicated by Adjudication Committee) was reported. Major CV event was defined as any of the following: CV death \[defined as sudden cardiac death, fatal myocardial infarction (MI), death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other CV causes\] non-fatal MI, non-fatal stroke, and hospitalization for unstable angina needing urgent revascularization. Event rate was calculated as the number of events per 100 participant-years at risk. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of All-cause Death, Non-fatal Myocardial Infraction (MI), Non-fatal Stroke or Hospitalization for Unstable Angina Needing Urgent Revascularization | From baseline until the date of first adjudicated and confirmed occurrence of all-cause death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina needing urgent revascularization (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for first occurrence of composite endpoint of all-cause death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina needing urgent revascularization (adjudicated by Adjudication Committee) was reported. All-cause death was defined as the death due to any cause during the course of study. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of All-cause Death, Non-fatal Myocardial Infarction (MI) or Non-fatal Stroke | From baseline until the date of first adjudicated and confirmed occurrence of all-cause death, non-fatal MI or non-fatal stroke (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for first occurrence of composite endpoint of all-cause death, non-fatal MI or non-fatal stroke (adjudicated by Adjudication Committee) was reported. All-cause death was defined as the death due to any cause during the course of study. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Unstable Angina Needing Urgent Revascularization | From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for unstable angina needing urgent revascularization (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for first occurrence of hospitalization for unstable angina needing urgent revascularization (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of Cardiovascular (CV) Death, Non-fatal Myocardial Infarction (MI), Non-fatal Stroke or Hospitalization for Unstable Angina | From baseline until the date of first adjudicated and confirmed occurrence of CV death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for first occurrence of composite endpoint of CV death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina (adjudicated by Adjudication Committee) was reported. CV death was defined as sudden cardiac death, fatal MI, death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other CV causes. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for Cardiovascular (CV) Death | From baseline until the date of adjudicated and confirmed occurrence of CV death (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for occurrence of CV death (adjudicated by Adjudication Committee) was reported. CV death was defined as sudden cardiac death, fatal MI, death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other CV causes. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for First Occurrence of Any Myocardial Infarction (Fatal or Non-fatal) | From baseline until the date of first adjudicated and confirmed occurrence of any myocardial infarction (fatal or non-fatal) (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for first occurrence of any myocardial infarction (fatal or non-fatal) (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for Fatal Myocardial Infarction (MI) | From baseline until the date of adjudicated and confirmed occurrence of fatal MI (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for occurrence of fatal MI (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for First Occurrence of Non-fatal Myocardial Infarction (MI) | From baseline until the date of first adjudicated and confirmed occurrence of non-fatal MI (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for first occurrence of non-fatal MI (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for First Occurrence of Any Stroke (Fatal or Non-fatal) | From baseline until the date of first adjudicated and confirmed occurrence of any stroke (fatal or non-fatal) (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for first occurrence of any stroke (fatal or non-fatal) (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for First Occurrence of Any Stroke (Fatal or Non-fatal), of Any Etiology | From baseline until the date of first adjudicated and confirmed occurrence of any stroke (fatal or non-fatal) of any etiology (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for first occurrence of any stroke (fatal or non-fatal) of any etiology (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for Fatal Stroke | From baseline until the date of adjudicated and confirmed occurrence of fatal stroke (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for occurrence of fatal stroke (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for First Occurrence of Non-fatal Stroke | From baseline until the date of first adjudicated and confirmed occurrence of non-fatal stroke (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for first occurrence of non-fatal stroke (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of Cardiovascular (CV) Death, Non-fatal Myocardial Infraction (MI) or Non-fatal Stroke | From baseline until the date of first adjudicated and confirmed occurrence of CV death, non-fatal MI or non-fatal stroke (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for first occurrence of composite endpoint of CV Death, non-fatal MI or non-fatal stroke (adjudicated by Adjudication Committee) was reported. CV death was defined as sudden cardiac death, fatal MI, death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other CV causes. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Congestive Heart Failure (CHF) | From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for CHF (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for first occurrence of hospitalization for CHF (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for First Occurrence of Coronary Revascularization | From baseline until the date of first adjudicated and confirmed occurrence of coronary revascularization (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for first occurrence of coronary revascularization (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for First Occurrence of Coronary Artery Bypass Graft Surgery (CABG) | From baseline until the date of first adjudicated and confirmed occurrence of CABG (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for first occurrence of CABG (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for First Occurrence of Percutaneous Coronary Intervention (PCI) | From baseline until the date of first adjudicated and confirmed occurrence of PCI (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for first occurrence of PCI (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for First Occurrence of Any Arterial Revascularizations | From baseline until the date of first adjudicated and confirmed occurrence of any arterial revascularizations (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for first occurrence of any arterial revascularizations (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Event Rate Per 100 Participant-years for All-cause Death | From baseline until the date of adjudicated and confirmed occurrence of all-cause death (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for occurrence of all-cause death (adjudicated by Adjudication Committee) was reported. All-cause death was defined as the death due to any cause during the course of study. Event rate was calculated as the number of events per 100 participant-years at risk. |
| Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 14 | Baseline, Week 14 | — |
| Nominal Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 14 | Baseline, Week 14 | — |
| Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Last Post-baseline Measurement | Baseline, last post-baseline measurement (any time up to Week 140) | — |
| Percent Change From Baseline in Lipid Levels at Week 14 | Baseline, Week 14 | Lipids included non-high density lipoprotein cholesterol (non-HDL-C), very low density lipoprotein cholesterol (VLDL-C), remnant lipoprotein cholesterol (RLP-C), apolipoprotein B (Apo B), HDL-C, apolipoprotein A-I (Apo A-I) and total cholesterol. |
| Percent Change From Baseline in Log-transformed Triglycerides and Lipoprotein (a) (Lp[a]) at Week 14 | Baseline, Week 14 | — |
| Percent Change From Baseline in Log-transformed High Sensitivity C-Reactive Protein (Hs-CRP) at Week 14 | Baseline, Week 14 | — |
| Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Unstable Angina | From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for unstable angina (maximum duration: up to 3.4 years) | Event rate per 100 participant-years for first occurrence of hospitalization for unstable angina (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, Colombia, Czechia, Denmark, Finland, France, Germany, Hungary, India, Ireland, Israel, Italy, Mexico, Netherlands, New Zealand, Poland, Puerto Rico, Romania, Russia, Slovakia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
The trial was terminated prematurely on November 1, 2016, due to the emerging clinical profile and the evolving treatment and market landscape for lipid-lowering agents.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose. | 5,283 |
| Bococizumab (PF-04950615) Participants received single dose of PF-04950615, 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3 years. Participants were followed up to 40 days after the last dose. | 5,281 |
| Total | 10,564 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 6 |
| Overall Study | Death | 61 | 54 |
| Overall Study | Lost to Follow-up | 81 | 86 |
| Overall Study | Other | 6 | 9 |
| Overall Study | Randomized, not treated | 4 | 5 |
| Overall Study | Withdrawal by Subject | 90 | 76 |
Baseline characteristics
| Characteristic | Bococizumab (PF-04950615) | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 62.2 Years STANDARD_DEVIATION 9.6 | 62.4 Years STANDARD_DEVIATION 9.6 | 62.5 Years STANDARD_DEVIATION 9.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 892 Participants | 1744 Participants | 852 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4387 Participants | 8817 Participants | 4430 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 105 Participants | 223 Participants | 118 Participants |
| Race (NIH/OMB) Black or African American | 252 Participants | 498 Participants | 246 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 140 Participants | 283 Participants | 143 Participants |
| Race (NIH/OMB) White | 4784 Participants | 9560 Participants | 4776 Participants |
| Sex: Female, Male Female | 1792 Participants | 3641 Participants | 1849 Participants |
| Sex: Female, Male Male | 3489 Participants | 6923 Participants | 3434 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 61 / 5,279 | 54 / 5,276 |
| other Total, other adverse events | 2,128 / 5,279 | 2,453 / 5,276 |
| serious Total, serious adverse events | 994 / 5,279 | 934 / 5,276 |
Outcome results
Primary
Event Rate Per 100 Participant-years for First Occurrence of Major Cardiovascular (CV) Event
Event rate per 100 participant-years for first occurrence of major CV event (adjudicated by Adjudication Committee) was reported. Major CV event was defined as any of the following: CV death \[defined as sudden cardiac death, fatal myocardial infarction (MI), death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other CV causes\] non-fatal MI, non-fatal stroke, and hospitalization for unstable angina needing urgent revascularization. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of first adjudicated and confirmed occurrence of major CV event (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for First Occurrence of Major Cardiovascular (CV) Event | 4.19 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for First Occurrence of Major Cardiovascular (CV) Event | 3.33 Events per 100 participant-years |
Comparison: Hazard ratio and 95% Confidence Interval (CI) were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.02146995% CI: [0.65, 0.97]Log Rank
Secondary
Event Rate Per 100 Participant-years for All-cause Death
Event rate per 100 participant-years for occurrence of all-cause death (adjudicated by Adjudication Committee) was reported. All-cause death was defined as the death due to any cause during the course of study. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of adjudicated and confirmed occurrence of all-cause death (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for All-cause Death | 1.06 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for All-cause Death | 0.97 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.62615795% CI: [0.63, 1.32]Log Rank
Secondary
Event Rate Per 100 Participant-years for Cardiovascular (CV) Death
Event rate per 100 participant-years for occurrence of CV death (adjudicated by Adjudication Committee) was reported. CV death was defined as sudden cardiac death, fatal MI, death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other CV causes. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of adjudicated and confirmed occurrence of CV death (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for Cardiovascular (CV) Death | 0.62 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for Cardiovascular (CV) Death | 0.51 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.44603395% CI: [0.5, 1.36]Log Rank
Secondary
Event Rate Per 100 Participant-years for Fatal Myocardial Infarction (MI)
Event rate per 100 participant-years for occurrence of fatal MI (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of adjudicated and confirmed occurrence of fatal MI (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for Fatal Myocardial Infarction (MI) | 0.16 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for Fatal Myocardial Infarction (MI) | 0.07 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.16261595% CI: [0.14, 1.44]Log Rank
Secondary
Event Rate Per 100 Participant-years for Fatal Stroke
Event rate per 100 participant-years for occurrence of fatal stroke (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of adjudicated and confirmed occurrence of fatal stroke (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for Fatal Stroke | 0.00 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for Fatal Stroke | 0.00 Events per 100 participant-years |
Secondary
Event Rate Per 100 Participant-years for First Occurrence of Any Arterial Revascularizations
Event rate per 100 participant-years for first occurrence of any arterial revascularizations (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of first adjudicated and confirmed occurrence of any arterial revascularizations (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for First Occurrence of Any Arterial Revascularizations | 1.51 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for First Occurrence of Any Arterial Revascularizations | 1.44 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.74897595% CI: [0.7, 1.3]Log Rank
Secondary
Event Rate Per 100 Participant-years for First Occurrence of Any Myocardial Infarction (Fatal or Non-fatal)
Event rate per 100 participant-years for first occurrence of any myocardial infarction (fatal or non-fatal) (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of first adjudicated and confirmed occurrence of any myocardial infarction (fatal or non-fatal) (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for First Occurrence of Any Myocardial Infarction (Fatal or Non-fatal) | 2.39 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for First Occurrence of Any Myocardial Infarction (Fatal or Non-fatal) | 1.79 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.02997795% CI: [0.57, 0.97]Log Rank
Secondary
Event Rate Per 100 Participant-years for First Occurrence of Any Stroke (Fatal or Non-fatal)
Event rate per 100 participant-years for first occurrence of any stroke (fatal or non-fatal) (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of first adjudicated and confirmed occurrence of any stroke (fatal or non-fatal) (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for First Occurrence of Any Stroke (Fatal or Non-fatal) | 0.72 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for First Occurrence of Any Stroke (Fatal or Non-fatal) | 0.48 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.10499895% CI: [0.41, 1.09]Log Rank
Secondary
Event Rate Per 100 Participant-years for First Occurrence of Any Stroke (Fatal or Non-fatal), of Any Etiology
Event rate per 100 participant-years for first occurrence of any stroke (fatal or non-fatal) of any etiology (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of first adjudicated and confirmed occurrence of any stroke (fatal or non-fatal) of any etiology (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for First Occurrence of Any Stroke (Fatal or Non-fatal), of Any Etiology | 0.77 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for First Occurrence of Any Stroke (Fatal or Non-fatal), of Any Etiology | 0.61 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.29433195% CI: [0.5, 1.24]Log Rank
Secondary
Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of All-cause Death, Non-fatal Myocardial Infarction (MI) or Non-fatal Stroke
Event rate per 100 participant-years for first occurrence of composite endpoint of all-cause death, non-fatal MI or non-fatal stroke (adjudicated by Adjudication Committee) was reported. All-cause death was defined as the death due to any cause during the course of study. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of first adjudicated and confirmed occurrence of all-cause death, non-fatal MI or non-fatal stroke (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of All-cause Death, Non-fatal Myocardial Infarction (MI) or Non-fatal Stroke | 3.97 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of All-cause Death, Non-fatal Myocardial Infarction (MI) or Non-fatal Stroke | 3.09 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.01569495% CI: [0.64, 0.95]Log Rank
Secondary
Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of All-cause Death, Non-fatal Myocardial Infraction (MI), Non-fatal Stroke or Hospitalization for Unstable Angina Needing Urgent Revascularization
Event rate per 100 participant-years for first occurrence of composite endpoint of all-cause death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina needing urgent revascularization (adjudicated by Adjudication Committee) was reported. All-cause death was defined as the death due to any cause during the course of study. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of first adjudicated and confirmed occurrence of all-cause death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina needing urgent revascularization (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of All-cause Death, Non-fatal Myocardial Infraction (MI), Non-fatal Stroke or Hospitalization for Unstable Angina Needing Urgent Revascularization | 4.59 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of All-cause Death, Non-fatal Myocardial Infraction (MI), Non-fatal Stroke or Hospitalization for Unstable Angina Needing Urgent Revascularization | 3.76 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.03595895% CI: [0.68, 0.99]Log Rank
Secondary
Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of Cardiovascular (CV) Death, Non-fatal Myocardial Infarction (MI), Non-fatal Stroke or Hospitalization for Unstable Angina
Event rate per 100 participant-years for first occurrence of composite endpoint of CV death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina (adjudicated by Adjudication Committee) was reported. CV death was defined as sudden cardiac death, fatal MI, death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other CV causes. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of first adjudicated and confirmed occurrence of CV death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of Cardiovascular (CV) Death, Non-fatal Myocardial Infarction (MI), Non-fatal Stroke or Hospitalization for Unstable Angina | 4.35 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of Cardiovascular (CV) Death, Non-fatal Myocardial Infarction (MI), Non-fatal Stroke or Hospitalization for Unstable Angina | 3.45 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.01805395% CI: [0.65, 0.96]Log Rank
Secondary
Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of Cardiovascular (CV) Death, Non-fatal Myocardial Infraction (MI) or Non-fatal Stroke
Event rate per 100 participant-years for first occurrence of composite endpoint of CV Death, non-fatal MI or non-fatal stroke (adjudicated by Adjudication Committee) was reported. CV death was defined as sudden cardiac death, fatal MI, death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other CV causes. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of first adjudicated and confirmed occurrence of CV death, non-fatal MI or non-fatal stroke (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of Cardiovascular (CV) Death, Non-fatal Myocardial Infraction (MI) or Non-fatal Stroke | 3.58 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for First Occurrence of Composite Endpoint of Cardiovascular (CV) Death, Non-fatal Myocardial Infraction (MI) or Non-fatal Stroke | 2.67 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.00759795% CI: [0.6, 0.93]Log Rank
Secondary
Event Rate Per 100 Participant-years for First Occurrence of Coronary Artery Bypass Graft Surgery (CABG)
Event rate per 100 participant-years for first occurrence of CABG (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of first adjudicated and confirmed occurrence of CABG (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for First Occurrence of Coronary Artery Bypass Graft Surgery (CABG) | 0.48 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for First Occurrence of Coronary Artery Bypass Graft Surgery (CABG) | 0.57 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.50984795% CI: [0.71, 2.01]Log Rank
Secondary
Event Rate Per 100 Participant-years for First Occurrence of Coronary Revascularization
Event rate per 100 participant-years for first occurrence of coronary revascularization (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of first adjudicated and confirmed occurrence of coronary revascularization (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for First Occurrence of Coronary Revascularization | 4.18 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for First Occurrence of Coronary Revascularization | 3.23 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.01045795% CI: [0.63, 0.94]Log Rank
Secondary
Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Congestive Heart Failure (CHF)
Event rate per 100 participant-years for first occurrence of hospitalization for CHF (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for CHF (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Congestive Heart Failure (CHF) | 0.75 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Congestive Heart Failure (CHF) | 0.83 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.67806195% CI: [0.72, 1.67]Log Rank
Secondary
Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Unstable Angina
Event rate per 100 participant-years for first occurrence of hospitalization for unstable angina (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for unstable angina (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Unstable Angina | 0.94 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Unstable Angina | 0.85 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.601295% CI: [0.6, 1.34]Log Rank
Secondary
Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Unstable Angina Needing Urgent Revascularization
Event rate per 100 participant-years for first occurrence of hospitalization for unstable angina needing urgent revascularization (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for unstable angina needing urgent revascularization (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Unstable Angina Needing Urgent Revascularization | 0.77 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Unstable Angina Needing Urgent Revascularization | 0.73 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.81422495% CI: [0.62, 1.46]Log Rank
Secondary
Event Rate Per 100 Participant-years for First Occurrence of Non-fatal Myocardial Infarction (MI)
Event rate per 100 participant-years for first occurrence of non-fatal MI (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of first adjudicated and confirmed occurrence of non-fatal MI (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for First Occurrence of Non-fatal Myocardial Infarction (MI) | 2.26 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for First Occurrence of Non-fatal Myocardial Infarction (MI) | 1.74 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.05153495% CI: [0.59, 1]Log Rank
Secondary
Event Rate Per 100 Participant-years for First Occurrence of Non-fatal Stroke
Event rate per 100 participant-years for first occurrence of non-fatal stroke (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of first adjudicated and confirmed occurrence of non-fatal stroke (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for First Occurrence of Non-fatal Stroke | 0.72 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for First Occurrence of Non-fatal Stroke | 0.48 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.10499895% CI: [0.41, 1.09]Log Rank
Secondary
Event Rate Per 100 Participant-years for First Occurrence of Percutaneous Coronary Intervention (PCI)
Event rate per 100 participant-years for first occurrence of PCI (adjudicated by Adjudication Committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.
Time frame: From baseline until the date of first adjudicated and confirmed occurrence of PCI (maximum duration: up to 3.4 years)
Population: FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to be randomized in more than 1 CV outcomes trial and all participants enrolled at study Site 3027 where a quality-related event was identified.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Event Rate Per 100 Participant-years for First Occurrence of Percutaneous Coronary Intervention (PCI) | 3.73 Events per 100 participant-years |
| Bococizumab (PF-04950615) | Event Rate Per 100 Participant-years for First Occurrence of Percutaneous Coronary Intervention (PCI) | 2.70 Events per 100 participant-years |
Comparison: Hazard ratio and 95% CI were obtained from a Cox proportional hazards model stratified by geographic region and complete statin intolerance with treatment as a covariate.p-value: 0.00298195% CI: [0.58, 0.9]Log Rank
Secondary
Nominal Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 14
Time frame: Baseline, Week 14
Population: Analysis was performed on FAS. Here, N signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Nominal Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 14 | 0.69 mg/dL | Standard Error 0.47 |
| Bococizumab (PF-04950615) | Nominal Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 14 | -73.11 mg/dL | Standard Error 0.47 |
Comparison: LS mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographic region and complete statin intolerance.p-value: <0.00195% CI: [-75.11, -72.5]MMRM
Secondary
Percent Change From Baseline in Lipid Levels at Week 14
Lipids included non-high density lipoprotein cholesterol (non-HDL-C), very low density lipoprotein cholesterol (VLDL-C), remnant lipoprotein cholesterol (RLP-C), apolipoprotein B (Apo B), HDL-C, apolipoprotein A-I (Apo A-I) and total cholesterol.
Time frame: Baseline, Week 14
Population: FAS population. Here, number analyzed n signifies number of participants who were evaluable for the specified categories.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Lipid Levels at Week 14 | RLP-C | 8.76 Percent change | Standard Error 0.81 |
| Placebo | Percent Change From Baseline in Lipid Levels at Week 14 | HDL-C | 1.05 Percent change | Standard Error 0.21 |
| Placebo | Percent Change From Baseline in Lipid Levels at Week 14 | VLDL-C | 4.88 Percent change | Standard Error 0.56 |
| Placebo | Percent Change From Baseline in Lipid Levels at Week 14 | Apo A-I | 0.07 Percent change | Standard Error 0.18 |
| Placebo | Percent Change From Baseline in Lipid Levels at Week 14 | Apo B | 1.89 Percent change | Standard Error 0.35 |
| Placebo | Percent Change From Baseline in Lipid Levels at Week 14 | Total cholesterol | 1.26 Percent change | Standard Error 0.28 |
| Placebo | Percent Change From Baseline in Lipid Levels at Week 14 | Non-HDL-C | 1.82 Percent change | Standard Error 0.34 |
| Bococizumab (PF-04950615) | Percent Change From Baseline in Lipid Levels at Week 14 | Total cholesterol | -36.72 Percent change | Standard Error 0.28 |
| Bococizumab (PF-04950615) | Percent Change From Baseline in Lipid Levels at Week 14 | Non-HDL-C | -50.05 Percent change | Standard Error 0.34 |
| Bococizumab (PF-04950615) | Percent Change From Baseline in Lipid Levels at Week 14 | VLDL-C | -13.54 Percent change | Standard Error 0.56 |
| Bococizumab (PF-04950615) | Percent Change From Baseline in Lipid Levels at Week 14 | RLP-C | -20.44 Percent change | Standard Error 0.81 |
| Bococizumab (PF-04950615) | Percent Change From Baseline in Lipid Levels at Week 14 | Apo B | -49.51 Percent change | Standard Error 0.35 |
| Bococizumab (PF-04950615) | Percent Change From Baseline in Lipid Levels at Week 14 | HDL-C | 7.96 Percent change | Standard Error 0.21 |
| Bococizumab (PF-04950615) | Percent Change From Baseline in Lipid Levels at Week 14 | Apo A-I | 4.46 Percent change | Standard Error 0.18 |
Comparison: Non-HDLC: LS-mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographic region and complete statin intolerance.p-value: <0.00195% CI: [-52.81, -50.94]MMRM
Comparison: VLDL-C: LS-mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographic region and complete statin intolerance.p-value: <0.00195% CI: [-19.96, -16.86]MMRM
Comparison: RLP-C: LS-mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographic region and complete statin intolerance.p-value: <0.00195% CI: [-31.44, -26.96]MMRM
Comparison: Apo B: LS-mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 52 with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographic region and complete statin intolerance.p-value: <0.00195% CI: [-52.37, -50.42]MMRM
Comparison: HDL-C: LS-mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographic region and complete statin intolerance.p-value: <0.00195% CI: [6.33, 7.5]MMRM
Comparison: Apo A-I: LS-mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 52 with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographic region and complete statin intolerance.p-value: <0.00195% CI: [3.9, 4.9]MMRM
Comparison: Total cholesterol: LS-mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographic region and complete statin intolerance.p-value: <0.00195% CI: [-38.75, -37.22]MMRM
Secondary
Percent Change From Baseline in Log-transformed High Sensitivity C-Reactive Protein (Hs-CRP) at Week 14
Time frame: Baseline, Week 14
Population: Analysis was performed on FAS. Here, N signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Log-transformed High Sensitivity C-Reactive Protein (Hs-CRP) at Week 14 | -4.8 Percent change | Standard Deviation 83.68 |
| Bococizumab (PF-04950615) | Percent Change From Baseline in Log-transformed High Sensitivity C-Reactive Protein (Hs-CRP) at Week 14 | 0.3 Percent change | Standard Deviation 90.03 |
Comparison: LS-mean differences, associated 95% CI and p-values were from an MMRM model on the difference of log-transformed observations with fixed effects for treatment group, visit, treatment group\*visit interaction, log-transformed baseline value, log-transformed baseline value\*visit interaction, geographical region and complete statin intolerance.p-value: 0.00295% CI: [1.02, 1.09]MMRM
Secondary
Percent Change From Baseline in Log-transformed Triglycerides and Lipoprotein (a) (Lp[a]) at Week 14
Time frame: Baseline, Week 14
Population: FAS population. Here, number analyzed n signifies number of participants who were evaluable for the specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Log-transformed Triglycerides and Lipoprotein (a) (Lp[a]) at Week 14 | Lp(a) | -2.0 Percent change | Standard Deviation 31.03 |
| Placebo | Percent Change From Baseline in Log-transformed Triglycerides and Lipoprotein (a) (Lp[a]) at Week 14 | Triglycerides | -1.4 Percent change | Standard Deviation 34.55 |
| Bococizumab (PF-04950615) | Percent Change From Baseline in Log-transformed Triglycerides and Lipoprotein (a) (Lp[a]) at Week 14 | Lp(a) | -33.3 Percent change | Standard Deviation 31.21 |
| Bococizumab (PF-04950615) | Percent Change From Baseline in Log-transformed Triglycerides and Lipoprotein (a) (Lp[a]) at Week 14 | Triglycerides | -19.7 Percent change | Standard Deviation 30.71 |
Comparison: Triglycerides: LS-mean differences, associated 95% CI and p-values were from an MMRM model including observations through Week 70 on the difference of log-transformed observations with fixed effects for treatment group, visit, treatment group\*visit interaction, log-transformed baseline value, log-transformed baseline value\*visit interaction, geographical region and complete statin intolerance. The 95% CI was derived by exponentiating the LS-mean difference confidence interval from the log scale.p-value: <0.00195% CI: [0.81, 0.83]MMRM
Comparison: Lp(a): LS-mean differences, associated 95% CI and p-values were from an MMRM model on the Difference of log-transformed observations with fixed effects for treatment group, visit, a treatment group\*visit interaction, log-transformed baseline value, log-transformed baseline value\*visit interaction, geographical region and complete statin intolerance. The 95% CI was derived by exponentiating the LS-mean difference confidence interval from the log scale.p-value: <0.00195% CI: [0.67, 0.69]MMRM
Secondary
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Last Post-baseline Measurement
Time frame: Baseline, last post-baseline measurement (any time up to Week 140)
Population: Analysis was performed on FAS. Here, N signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Last Post-baseline Measurement | 2.90 Percent change | Standard Error 0.45 |
| Bococizumab (PF-04950615) | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Last Post-baseline Measurement | -36.41 Percent change | Standard Error 0.45 |
Comparison: LS-mean difference, associated 95% CI, and p-value were from an analysis of covariance (ANCOVA) model with fixed effects for treatment group, baseline value, geographic region and complete statin intolerance.p-value: <0.00195% CI: [-40.55, -38.06]ANCOVA
Secondary
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 14
Time frame: Baseline, Week 14
Population: Analysis was performed on FAS. Here, Number of participants analyzed (N) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 14 | 2.13 Percent change | Standard Error 0.36 |
| Bococizumab (PF-04950615) | Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 14 | -54.77 Percent change | Standard Error 0.36 |
Comparison: Least square (LS) mean differences, associated 95% CI, and p-values were from an mixed model repeated measures (MMRM) model including observations through Week 70 with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographic region and complete statin intolerance.p-value: <0.00195% CI: [-57.91, -55.89]MMRM