Trial Outcomes & Findings for The Evaluation of Bococizumab (PF-04950615;RN316) in Reducing the Occurrence of Major Cardiovascular Events in High Risk Subjects (NCT NCT01975376)

NCT ID: NCT01975376

Last Updated: 2018-07-11

Results Overview

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 cardiovascular 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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

16784 participants

Primary outcome timeframe

From baseline until the date of first adjudicated and confirmed occurrence of major CV event (maximum duration: up to 3.4 years)

Results posted on

2018-07-11

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Study STARTED	8390	8394
Overall Study Treated	8374	8386
Overall Study COMPLETED	8164	8177
Overall Study NOT COMPLETED	226	217

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Overall Study Adverse Event	5	5
Overall Study Death	65	72
Overall Study Lost to Follow-up	70	66
Overall Study Withdrew consent	68	62
Overall Study Other	2	4
Overall Study Randomized, Not Treated	16	8

Baseline Characteristics

The Evaluation of Bococizumab (PF-04950615;RN316) in Reducing the Occurrence of Major Cardiovascular Events in High Risk Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Total n=16784 Participants Total of all reporting groups
Age, Continuous	63.3 Years STANDARD_DEVIATION 9.2 • n=5 Participants	63.3 Years STANDARD_DEVIATION 9.1 • n=7 Participants	63.3 Years STANDARD_DEVIATION 9.1 • n=5 Participants
Sex: Female, Male Female	2223 Participants n=5 Participants	2207 Participants n=7 Participants	4430 Participants n=5 Participants
Sex: Female, Male Male	6167 Participants n=5 Participants	6187 Participants n=7 Participants	12354 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1758 Participants n=5 Participants	1746 Participants n=7 Participants	3504 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6631 Participants n=5 Participants	6642 Participants n=7 Participants	13273 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	354 Participants n=5 Participants	369 Participants n=7 Participants	723 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	392 Participants n=5 Participants	412 Participants n=7 Participants	804 Participants n=5 Participants
Race (NIH/OMB) White	7315 Participants n=5 Participants	7280 Participants n=7 Participants	14595 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	329 Participants n=5 Participants	333 Participants n=7 Participants	662 Participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline until the date of first adjudicated and confirmed occurrence of major CV event (maximum duration: up to 3.4 years)

Population: Full analysis set (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.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For First Occurrence of Major Cardiovascular (CV) Event	3.02 Events Per 100 Participant-Years Interval 2.59 to 3.51	3.01 Events Per 100 Participant-Years Interval 2.58 to 3.5

SECONDARY outcome

Timeframe: From baseline until the date of first adjudicated and confirmed occurrence of the 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.

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. Cardiovascular 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 cardiovascular causes. Event rate was calculated as the number of events per 100 participant-years at risk.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For First Occurrence of Composite Endpoint of Cardiovascular Death, Non-Fatal Myocardial Infraction, or Non-Fatal Stroke	2.49 Events Per 100 Participant-Years Interval 2.1 to 2.93	2.59 Events Per 100 Participant-Years Interval 2.19 to 3.04

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For First Occurrence of Composite Endpoint of All-Cause Death, Non-Fatal Myocardial Infraction, Non-Fatal Stroke, or Hospitalization for Unstable Angina Needing Urgent Revascularization	3.51 Events Per 100 Participant-Years Interval 3.04 to 4.03	3.48 Events Per 100 Participant-Years Interval 3.02 to 4.0

SECONDARY outcome

Timeframe: From baseline until the date of first adjudicated and confirmed occurrence of the 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.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For First Occurrence of Composite Endpoint of All-Cause Death, Non-Fatal Myocardial Infarction, or Non-Fatal Stroke	2.98 Events Per 100 Participant-Years Interval 2.55 to 3.46	3.06 Events Per 100 Participant-Years Interval 2.62 to 3.54

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For First Occurrence of Hospitalization for Unstable Angina Needing Urgent Revascularization	0.57 Events Per 100 Participant-Years Interval 0.39 to 0.8	0.47 Events Per 100 Participant-Years Interval 0.31 to 0.68

SECONDARY outcome

Timeframe: From baseline until the date of first adjudicated and confirmed occurrence of cardiovascular death, non-fatal MI, non-fatal stroke and hospitalization for unstable angina (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of composite endpoint of cardiovascular death, non-fatal MI, non-fatal stroke and hospitalization for unstable angina (adjudicated by adjudication committee) was reported. Cardiovascular 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 cardiovascular causes. Event rate was calculated as the number of events per 100 participant-years at risk.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For First Occurrence of Composite Endpoint of Cardiovascular Death, Non-Fatal Myocardial Infarction, Non-Fatal Stroke and Hospitalization for Unstable Angina	3.22 Events Per 100 Participant-Years Interval 2.77 to 3.72	3.19 Events Per 100 Participant-Years Interval 2.74 to 3.69

SECONDARY outcome

Timeframe: From baseline until the date of adjudicated and confirmed occurrence of cardiovascular death (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for cardiovascular death (adjudicated by adjudication committee) was reported. Cardiovascular 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 cardiovascular causes. Event rate was calculated as the number of events per 100 participant-years at risk.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For Cardiovascular Death	0.52 Events Per 100 Participant-Years Interval 0.35 to 0.74	0.64 Events Per 100 Participant-Years Interval 0.45 to 0.88

SECONDARY outcome

Timeframe: From baseline until the date of first adjudicated and confirmed occurrence of any MI (fatal or non-fatal) (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for first occurrence of any MI (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.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For First Occurrence of Any Myocardial Infarction (Fatal or Non-Fatal)	1.56 Events Per 100 Participant-Years Interval 1.26 to 1.92	1.74 Events Per 100 Participant-Years Interval 1.41 to 2.11

SECONDARY outcome

Timeframe: 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 fatal MI (adjudicated by adjudication committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For Fatal Myocardial Infarction	0.03 Events Per 100 Participant-Years Interval 0.0 to 0.12	0.05 Events Per 100 Participant-Years Interval 0.01 to 0.15

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For First Occurrence of Non-Fatal Myocardial Infarction	1.53 Events Per 100 Participant-Years Interval 1.23 to 1.88	1.70 Events Per 100 Participant-Years Interval 1.38 to 2.07

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For First Occurrence of Any Stroke (Fatal or Non-Fatal)	0.71 Events Per 100 Participant-Years Interval 0.51 to 0.96	0.38 Events Per 100 Participant-Years Interval 0.24 to 0.57

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For First Occurrence of Any Stroke (Fatal or Non-Fatal), of Any Etiology	0.79 Events Per 100 Participant-Years Interval 0.58 to 1.06	0.43 Events Per 100 Participant-Years Interval 0.28 to 0.64

SECONDARY outcome

Timeframe: From baseline until the date of first adjudicated and confirmed occurrence of fatal stroke (maximum duration: up to 3.4 years)

Event rate per 100 participant-years for fatal stroke (adjudicated by adjudication committee) was reported. Event rate was calculated as the number of events per 100 participant-years at risk.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For Fatal Stroke	0.10 Events Per 100 Participant-Years Interval 0.04 to 0.22	0.05 Events Per 100 Participant-Years Interval 0.01 to 0.15

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For First Occurrence of Non-Fatal Stroke	0.62 Events Per 100 Participant-Years Interval 0.44 to 0.86	0.33 Events Per 100 Participant-Years Interval 0.2 to 0.51

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For First Occurrence of Hospitalization for Unstable Angina	0.78 Events Per 100 Participant-Years Interval 0.57 to 1.04	0.64 Events Per 100 Participant-Years Interval 0.45 to 0.88

SECONDARY outcome

Timeframe: From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for congestive heart failure (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.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For First Occurrence of Hospitalization for Congestive Heart Failure (CHF)	0.81 Events Per 100 Participant-Years Interval 0.6 to 1.08	0.69 Events Per 100 Participant-Years Interval 0.49 to 0.94

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For First Occurrence of Coronary Revascularization	2.74 Events Per 100 Participant-Years Interval 2.33 to 3.2	2.45 Events Per 100 Participant-Years Interval 2.06 to 2.89

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For First Occurrence of Coronary Artery Bypass Graft Surgery (CABG)	0.40 Events Per 100 Participant-Years Interval 0.25 to 0.6	0.41 Events Per 100 Participant-Years Interval 0.26 to 0.61

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For First Occurrence of Percutaneous Coronary Intervention (PCI)	2.37 Events Per 100 Participant-Years Interval 1.99 to 2.8	2.08 Events Per 100 Participant-Years Interval 1.73 to 2.49

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For First Occurrence of Any Arterial Revascularizations	1.26 Events Per 100 Participant-Years Interval 0.99 to 1.59	1.28 Events Per 100 Participant-Years Interval 1.0 to 1.61

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Event Rate Per 100 Participant-Years For All-Cause Death	1.00 Events Per 100 Participant-Years Interval 0.76 to 1.29	1.13 Events Per 100 Participant-Years Interval 0.88 to 1.44

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=6448 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=6439 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 14	3.40 Percent change Standard Error 0.31	-57.17 Percent change Standard Error 0.31

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: Analysis was performed on FAS. Here, "N" signifies number of participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Placebo n=6448 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=6439 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Nominal Change From Baseline in Low Density Lipoprotein Cholesterol at Week 14	2.33 mg/dL Standard Error 0.28	-52.37 mg/dL Standard Error 0.28

SECONDARY outcome

Timeframe: Baseline, last post-baseline measurement (any time up to Week 140)

Population: Analysis was performed on FAS. Here, "N" signifies number of participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Placebo n=8240 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8254 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Last Post-Baseline Measurement	5.05 Percent Change Standard Error 0.35	-41.67 Percent Change Standard Error 0.35

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: Analysis was performed on FAS. Here, number analyzed "n" signifies number of participants who were evaluable for the specified categories.

Lipids included non-high density lipoprotein cholesterol (non-HDL-C), total cholesterol, very low density lipoprotein cholesterol (VLDL-C), remnant lipoprotein cholesterol (RLP-C), apolipoprotein B (Apo B), HDL-C and apolipoprotein A-I (Apo A-I).

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Percent Change From Baseline in Lipid Levels at Week 14 Non - HDL-C	3.21 Percent Change Standard Error 0.28	-51.66 Percent Change Standard Error 0.28
Percent Change From Baseline in Lipid Levels at Week 14 Total cholesterol	2.38 Percent Change Standard Error 0.20	-34.13 Percent Change Standard Error 0.20
Percent Change From Baseline in Lipid Levels at Week 14 VLDL - C	6.52 Percent Change Standard Error 0.45	-13.65 Percent Change Standard Error 0.45
Percent Change From Baseline in Lipid Levels at Week 14 RLP - C	9.23 Percent Change Standard Error 0.79	-21.02 Percent Change Standard Error 0.79
Percent Change From Baseline in Lipid Levels at Week 14 Apo B	2.80 Percent Change Standard Error 0.31	-55.76 Percent Change Standard Error 0.31
Percent Change From Baseline in Lipid Levels at Week 14 HDL - C	1.19 Percent Change Standard Error 0.16	7.33 Percent Change Standard Error 0.16
Percent Change From Baseline in Lipid Levels at Week 14 Apo A - I	1.21 Percent Change Standard Error 0.18	4.74 Percent Change Standard Error 0.18

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: Analysis was performed on FAS. Here, number analyzed "n" signifies number of participants who were evaluable for the specified categories.

Outcome measures

Outcome measures
Measure	Placebo n=8390 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8394 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Percent Change From Baseline in Log-Transformed Lipoprotein (a) (Lp[a]) and Triglycerides at Week 14 Lp (a)	-1.3 Percent Change Standard Deviation 28.81	-33.9 Percent Change Standard Deviation 29.62
Percent Change From Baseline in Log-Transformed Lipoprotein (a) (Lp[a]) and Triglycerides at Week 14 Triglycerides	0.6 Percent Change Standard Deviation 32.84	-18.9 Percent Change Standard Deviation 28.44

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: Analysis was performed on FAS. Here, "N" signifies number of participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Placebo n=5931 Participants Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=5930 Participants Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Percent Change From Baseline in Log-Transformed High Sensitivity C-Reactive Protein (Hs-CRP) at Week 14	-6.5 Percent change Standard Deviation 88.28	-1.1 Percent change Standard Deviation 91.91

Adverse Events

Placebo

Serious events: 986 serious events

Other events: 1570 other events

Deaths: 65 deaths

Bococizumab (PF-04950615)

Serious events: 1060 serious events

Other events: 2015 other events

Deaths: 72 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=8374 participants at risk Participants received single dose of placebo matched to PF-04950615 subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.	Bococizumab (PF-04950615) n=8386 participants at risk Participants received single dose of PF-04950615 150 milligrams, subcutaneous injection once every 2 weeks for upto 3 years. Participants were followed up to 40 days after the last dose.
Gastrointestinal disorders Diarrhoea	1.6% 133/8374 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified	2.0% 169/8386 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified
General disorders Injection site reaction	1.1% 88/8374 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified	7.0% 588/8386 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified
Infections and infestations Nasopharyngitis	3.5% 289/8374 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified	3.4% 283/8386 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified
Infections and infestations Upper respiratory tract infection	2.3% 193/8374 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified	2.2% 183/8386 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified
Metabolism and nutrition disorders Type 2 diabetes mellitus	2.3% 195/8374 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified	2.6% 217/8386 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified
Musculoskeletal and connective tissue disorders Arthralgia	2.4% 197/8374 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified	2.5% 208/8386 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified
Musculoskeletal and connective tissue disorders Back pain	2.4% 203/8374 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified	2.6% 217/8386 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified
Musculoskeletal and connective tissue disorders Myalgia	1.9% 160/8374 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified	2.0% 170/8386 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified
Nervous system disorders Headache	1.6% 136/8374 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified	2.0% 171/8386 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified
Vascular disorders Hypertension	3.6% 303/8374 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified	3.2% 270/8386 • Baseline up to 3.4 years Safety analysis set: all participants who randomized, had atleast 1 dose of study drug, excluding those attempted to randomize more than once in a bococizumab CV outcomes trial (B1481022/B1481038) or attempted to randomize in more than 1 CV outcomes trial, and all participants enrolled at study Site 3027 where a quality-related event was identified

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER