Trial Outcomes & Findings for The Evaluation of Bococizumab (PF-04950615; RN316) in Reducing the Occurrence of Major Cardiovascular Events in High Risk Subjects (NCT NCT01975389)

NCT ID: NCT01975389

Last Updated: 2019-05-01

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 \[defined as sudden cardiac death, fatal myocardial infarction (MI), death due to heart failure, death due to stroke (fatal ischemic stroke or fatal stroke of undetermined etiology), or death due to other CV causes\] 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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

10564 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

2019-05-01

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	5283	5281
Overall Study Treated	5279	5276
Overall Study COMPLETED	5031	5045
Overall Study NOT COMPLETED	252	236

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Adverse Event	10	6
Overall Study Death	61	54
Overall Study Lost to Follow-up	81	86
Overall Study Withdrawal by Subject	90	76
Overall Study Other	6	9
Overall Study Randomized, not treated	4	5

Baseline Characteristics

Full analysis set (FAS): all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.	Total n=10564 Participants Total of all reporting groups
Age, Continuous	62.5 Years STANDARD_DEVIATION 9.5 • n=5 Participants	62.2 Years STANDARD_DEVIATION 9.6 • n=7 Participants	62.4 Years STANDARD_DEVIATION 9.6 • n=5 Participants
Sex: Female, Male Female	1849 Participants n=5 Participants	1792 Participants n=7 Participants	3641 Participants n=5 Participants
Sex: Female, Male Male	3434 Participants n=5 Participants	3489 Participants n=7 Participants	6923 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	852 Participants n=5 Participants • Full analysis set (FAS): all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	892 Participants n=7 Participants • Full analysis set (FAS): all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	1744 Participants n=5 Participants • Full analysis set (FAS): all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.
Ethnicity (NIH/OMB) Not Hispanic or Latino	4430 Participants n=5 Participants • Full analysis set (FAS): all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	4387 Participants n=7 Participants • Full analysis set (FAS): all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	8817 Participants n=5 Participants • Full analysis set (FAS): all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants • Full analysis set (FAS): all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	2 Participants n=7 Participants • Full analysis set (FAS): all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	3 Participants n=5 Participants • Full analysis set (FAS): all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	0 Participants n=7 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	0 Participants n=5 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.
Race (NIH/OMB) Asian	118 Participants n=5 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	105 Participants n=7 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	223 Participants n=5 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	0 Participants n=7 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	0 Participants n=5 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.
Race (NIH/OMB) Black or African American	246 Participants n=5 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	252 Participants n=7 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	498 Participants n=5 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.
Race (NIH/OMB) White	4776 Participants n=5 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	4784 Participants n=7 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	9560 Participants n=5 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.
Race (NIH/OMB) More than one race	0 Participants n=5 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	0 Participants n=7 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	0 Participants n=5 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.
Race (NIH/OMB) Unknown or Not Reported	143 Participants n=5 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	140 Participants n=7 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.	283 Participants n=5 Participants • FAS: all participants who were randomized, excluding who attempted to be randomized more than once into a bococizumab cardiovascular (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.

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: 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=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
Event Rate Per 100 Participant-years for First Occurrence of Major Cardiovascular (CV) Event	4.19 Events per 100 participant-years Interval 3.66 to 4.78	3.33 Events per 100 participant-years Interval 2.86 to 3.86

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
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 Interval 3.09 to 4.12	2.67 Events per 100 participant-years Interval 2.25 to 3.14

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=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
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 Interval 4.03 to 5.2	3.76 Events per 100 participant-years Interval 3.26 to 4.32

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
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 Interval 3.45 to 4.54	3.09 Events per 100 participant-years Interval 2.64 to 3.6

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=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Unstable Angina Needing Urgent Revascularization	0.77 Events per 100 participant-years Interval 0.56 to 1.05	0.73 Events per 100 participant-years Interval 0.52 to 1.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
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 Interval 3.81 to 4.94	3.45 Events per 100 participant-years Interval 2.97 to 3.98

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
Event Rate Per 100 Participant-years for Cardiovascular (CV) Death	0.62 Events per 100 participant-years Interval 0.43 to 0.87	0.51 Events per 100 participant-years Interval 0.34 to 0.74

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
Event Rate Per 100 Participant-years for First Occurrence of Any Myocardial Infarction (Fatal or Non-fatal)	2.39 Events per 100 participant-years Interval 2.0 to 2.84	1.79 Events per 100 participant-years Interval 1.45 to 2.19

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 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.

Outcome measures

Outcome measures
Measure	Placebo n=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
Event Rate Per 100 Participant-years for Fatal Myocardial Infarction (MI)	0.16 Events per 100 participant-years Interval 0.08 to 0.31	0.07 Events per 100 participant-years Interval 0.02 to 0.19

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=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
Event Rate Per 100 Participant-years for First Occurrence of Non-fatal Myocardial Infarction (MI)	2.26 Events per 100 participant-years Interval 1.88 to 2.7	1.74 Events per 100 participant-years Interval 1.4 to 2.12

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=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
Event Rate Per 100 Participant-years for First Occurrence of Any Stroke (Fatal or Non-fatal)	0.72 Events per 100 participant-years Interval 0.51 to 0.98	0.48 Events per 100 participant-years Interval 0.31 to 0.7

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=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
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 Interval 0.56 to 1.04	0.61 Events per 100 participant-years Interval 0.42 to 0.85

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
Event Rate Per 100 Participant-years for Fatal Stroke	0.00 Events per 100 participant-years Interval 0.0 to 0.05	0.00 Events per 100 participant-years Interval 0.0 to 0.05

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=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
Event Rate Per 100 Participant-years for First Occurrence of Non-fatal Stroke	0.72 Events per 100 participant-years Interval 0.51 to 0.98	0.48 Events per 100 participant-years Interval 0.31 to 0.7

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=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Unstable Angina	0.94 Events per 100 participant-years Interval 0.7 to 1.24	0.85 Events per 100 participant-years Interval 0.62 to 1.13

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
Event Rate Per 100 Participant-years for First Occurrence of Hospitalization for Congestive Heart Failure (CHF)	0.75 Events per 100 participant-years Interval 0.54 to 1.02	0.83 Events per 100 participant-years Interval 0.6 to 1.11

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=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
Event Rate Per 100 Participant-years for First Occurrence of Coronary Revascularization	4.18 Events per 100 participant-years Interval 3.65 to 4.77	3.23 Events per 100 participant-years Interval 2.76 to 3.75

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=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
Event Rate Per 100 Participant-years for First Occurrence of Coronary Artery Bypass Graft Surgery (CABG)	0.48 Events per 100 participant-years Interval 0.31 to 0.7	0.57 Events per 100 participant-years Interval 0.39 to 0.81

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=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
Event Rate Per 100 Participant-years for First Occurrence of Percutaneous Coronary Intervention (PCI)	3.73 Events per 100 participant-years Interval 3.23 to 4.28	2.70 Events per 100 participant-years Interval 2.27 to 3.17

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=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
Event Rate Per 100 Participant-years for First Occurrence of Any Arterial Revascularizations	1.51 Events per 100 participant-years Interval 1.2 to 1.88	1.44 Events per 100 participant-years Interval 1.14 to 1.8

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 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.

Outcome measures

Outcome measures
Measure	Placebo n=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
Event Rate Per 100 Participant-years for All-cause Death	1.06 Events per 100 participant-years Interval 0.81 to 1.37	0.97 Events per 100 participant-years Interval 0.73 to 1.27

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=4712 Participants 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.	Bococizumab (PF-04950615) n=4654 Participants 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.
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 14	2.13 Percent change Standard Error 0.36	-54.77 Percent change Standard Error 0.36

SECONDARY outcome

Timeframe: Baseline, Week 14

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

Outcome measures

Outcome measures
Measure	Placebo n=4712 Participants 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.	Bococizumab (PF-04950615) n=4654 Participants 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.
Nominal Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 14	0.69 mg/dL Standard Error 0.47	-73.11 mg/dL Standard Error 0.47

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=5242 Participants 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.	Bococizumab (PF-04950615) n=5246 Participants 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.
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Last Post-baseline Measurement	2.90 Percent change Standard Error 0.45	-36.41 Percent change Standard Error 0.45

SECONDARY outcome

Timeframe: Baseline, Week 14

Population: FAS population. 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), 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.

Outcome measures

Outcome measures
Measure	Placebo n=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
Percent Change From Baseline in Lipid Levels at Week 14 Non-HDL-C	1.82 Percent change Standard Error 0.34	-50.05 Percent change Standard Error 0.34
Percent Change From Baseline in Lipid Levels at Week 14 VLDL-C	4.88 Percent change Standard Error 0.56	-13.54 Percent change Standard Error 0.56
Percent Change From Baseline in Lipid Levels at Week 14 RLP-C	8.76 Percent change Standard Error 0.81	-20.44 Percent change Standard Error 0.81
Percent Change From Baseline in Lipid Levels at Week 14 Apo B	1.89 Percent change Standard Error 0.35	-49.51 Percent change Standard Error 0.35
Percent Change From Baseline in Lipid Levels at Week 14 HDL-C	1.05 Percent change Standard Error 0.21	7.96 Percent change Standard Error 0.21
Percent Change From Baseline in Lipid Levels at Week 14 Apo A-I	0.07 Percent change Standard Error 0.18	4.46 Percent change Standard Error 0.18
Percent Change From Baseline in Lipid Levels at Week 14 Total cholesterol	1.26 Percent change Standard Error 0.28	-36.72 Percent change Standard Error 0.28

SECONDARY outcome

Timeframe: Baseline, Week 14

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

Outcome measures

Outcome measures
Measure	Placebo n=5283 Participants 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.	Bococizumab (PF-04950615) n=5281 Participants 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.
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	-19.7 Percent change Standard Deviation 30.71
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	-33.3 Percent change Standard Deviation 31.21

SECONDARY outcome

Timeframe: Baseline, Week 14

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

Outcome measures

Outcome measures
Measure	Placebo n=4655 Participants 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.	Bococizumab (PF-04950615) n=4620 Participants 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.
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	0.3 Percent change Standard Deviation 90.03

Adverse Events

Placebo

Serious events: 994 serious events

Other events: 2128 other events

Deaths: 61 deaths

Bococizumab (PF-04950615)

Serious events: 934 serious events

Other events: 2453 other events

Deaths: 54 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

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