Clinical Trial Results:
Phase 3 Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel Group Evaluation of the Efficacy, Safety, and Tolerability of Bococizumab (PF-04950615), in Reducing the Occurrence of Major Cardiovascular Events in High Risk Subjects
Summary
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EudraCT number |
2013-002646-36 |
Trial protocol |
GB NL FI DE HU CZ SE SK ES IT BE DK PL IE |
Global end of trial date |
22 Mar 2017
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Results information
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Results version number |
v1 |
This version publication date |
10 Nov 2017
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First version publication date |
10 Nov 2017
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
B1481022
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01975376 | ||
WHO universal trial number (UTN) |
U1111-1151-0594 | ||
Sponsors
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Sponsor organisation name |
Pfizer, Inc.
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Sponsor organisation address |
235 E 42nd Street, New York, United States, 10017
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Public contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., Pfizer ClinicalTrials.gov Call Center, 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Scientific contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., Pfizer ClinicalTrials.gov Call Center, 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
14 Sep 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Mar 2017
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To demonstrate the superior efficacy of bococizumab compared with placebo in reducing the risk of major CV events, a composite endpoint which included adjudicated and confirmed CV death, non-fatal MI, non-fatal stroke, and hospitalization for unstable angina with urgent revascularization, in subjects at high or very high risk of major CV events who were on background lipid-lowering treatment and had an LDL-C >=70 mg/dL (1.81 mmol/L) or non-HDL-C >=100 mg/dL (2.59 mmol/L).
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Protection of trial subjects |
This study was conducted in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines and all local regulatory requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Oct 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 776
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Country: Number of subjects enrolled |
Australia: 165
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Country: Number of subjects enrolled |
Belgium: 166
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Country: Number of subjects enrolled |
Brazil: 1553
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Country: Number of subjects enrolled |
Canada: 482
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Country: Number of subjects enrolled |
Chile: 104
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Country: Number of subjects enrolled |
China: 338
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Country: Number of subjects enrolled |
Colombia: 228
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Country: Number of subjects enrolled |
Czech Republic: 310
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Country: Number of subjects enrolled |
Denmark: 328
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Country: Number of subjects enrolled |
Finland: 281
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Country: Number of subjects enrolled |
France: 190
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Country: Number of subjects enrolled |
Germany: 1029
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Country: Number of subjects enrolled |
Hungary: 413
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Country: Number of subjects enrolled |
Ireland: 8
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Country: Number of subjects enrolled |
Israel: 278
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Country: Number of subjects enrolled |
Italy: 71
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Country: Number of subjects enrolled |
Korea, Republic of: 104
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Country: Number of subjects enrolled |
Mexico: 367
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Country: Number of subjects enrolled |
Netherlands: 1016
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Country: Number of subjects enrolled |
New Zealand: 113
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Country: Number of subjects enrolled |
Poland: 1486
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Country: Number of subjects enrolled |
Puerto Rico: 28
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Country: Number of subjects enrolled |
Romania: 186
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Country: Number of subjects enrolled |
Russian Federation: 415
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Country: Number of subjects enrolled |
Slovakia: 439
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Country: Number of subjects enrolled |
South Africa: 453
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Country: Number of subjects enrolled |
Spain: 482
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Country: Number of subjects enrolled |
Sweden: 272
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Country: Number of subjects enrolled |
Switzerland: 64
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Country: Number of subjects enrolled |
Taiwan: 49
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Country: Number of subjects enrolled |
Thailand: 41
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Country: Number of subjects enrolled |
Turkey: 47
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Country: Number of subjects enrolled |
United Kingdom: 654
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Country: Number of subjects enrolled |
United States: 3848
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Worldwide total number of subjects |
16784
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EEA total number of subjects |
7331
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
8994
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From 65 to 84 years |
7715
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85 years and over |
75
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Recruitment
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Recruitment details |
The trial was terminated prematurely on November 1, 2016, due to the emerging clinical profile and the evolving treatment and market landscape for lipid-lowering agents. | ||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Study was conducted at multiple sites from 29 October 2013 to 22 March 2017. However, subjects were screened from 29 October 2013 through 01 November 2016. | ||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Investigator, Carer, Subject | ||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||||||||
Arm description |
Subjects received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3.3 years. Subjects were followed up to 40 days after the last dose. | ||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Matched to PF-04950615 subcutaneous injection once in every 2 Weeks over a period of 3.3 years.
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Arm title
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Bococizumab (PF-04950615) | ||||||||||||||||||||||||||||||
Arm description |
Subjects received single dose of PF-04950615 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3.3 years. Subjects were followed up to 40 days after the last dose. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Bococizumab
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Investigational medicinal product code |
PF-04950615
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
150 milligrams, subcutaneous injection once in every 2 Weeks over a period of 3.3 years.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Subjects received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3.3 years. Subjects were followed up to 40 days after the last dose. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Bococizumab (PF-04950615)
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Reporting group description |
Subjects received single dose of PF-04950615 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3.3 years. Subjects were followed up to 40 days after the last dose. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Subjects received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3.3 years. Subjects were followed up to 40 days after the last dose. | ||
Reporting group title |
Bococizumab (PF-04950615)
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Reporting group description |
Subjects received single dose of PF-04950615 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3.3 years. Subjects were followed up to 40 days after the last dose. |
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End point title |
Event Rate Per 100 Subject-Years For First Occurrence of Major Cardiovascular (CV) Event | ||||||||||||
End point description |
Event rate per 100 Subject-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 Subject-years at risk. Full analysis set (FAS): all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
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End point type |
Primary
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End point timeframe |
From baseline until the date of first adjudicated and confirmed occurrence of major CV event (maximum duration: up to 3.3 years).
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Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95 percent (%) Confidence Interval (CI) were from a Cox proportional hazards model stratified by geographic region and Low density lipoprotein cholesterol (LDL-C) at pre-screening (less than [<] 100 milligrams per deciliters [mg/dL], greater than and equal to [>=] 100 mg/dL) with treatment as a co-variate.
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Comparison groups |
Placebo v Bococizumab (PF-04950615)
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Number of subjects included in analysis |
16784
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.930905 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.99
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.8 | ||||||||||||
upper limit |
1.22 |
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End point title |
Event rate per 100 Subject-years For First Occurrence of Composite Endpoint of Cardiovascular Death, Non-Fatal Myocardial Infraction, or Non-Fatal Stroke | ||||||||||||
End point description |
Cardiovascular death is 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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
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End point type |
Secondary
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End point timeframe |
From baseline until the date of first adjudicated and confirmed occurrence of the cardiovascular death, non-fatal MI or non-fatal stroke (maximum duration: up to 3.3 years)
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Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
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Comparison groups |
Placebo v Bococizumab (PF-04950615)
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Number of subjects included in analysis |
16784
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.784265 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.03
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.82 | ||||||||||||
upper limit |
1.3 |
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End point title |
Event rate per 100 Subject-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 | ||||||||||||
End point description |
Event rate per 100 Subject-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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
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End point type |
Secondary
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End point 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 3.3 years)
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Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
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Comparison groups |
Placebo v Bococizumab (PF-04950615)
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Number of subjects included in analysis |
16784
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.892441 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.99
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.81 | ||||||||||||
upper limit |
1.2 |
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End point title |
Event rate per 100 Subject-years For First Occurrence of Composite Endpoint of All-Cause Death, Non-Fatal Myocardial Infarction, or Non-Fatal Stroke | ||||||||||||
End point description |
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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
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End point type |
Secondary
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End point 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 3.3 years)
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Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
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Comparison groups |
Placebo v Bococizumab (PF-04950615)
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Number of subjects included in analysis |
16784
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.845797 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.02
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.83 | ||||||||||||
upper limit |
1.26 |
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End point title |
Event rate per 100 Subject-years For First Occurrence of Hospitalization for Unstable Angina Needing Urgent Revascularization | ||||||||||||
End point description |
Event rate per 100 participant-years for first occurrence of hospitalization for unstable angina needing urgent revascularization (adjudicated by Adjudication Committee) was reported. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
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End point type |
Secondary
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End point timeframe |
From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for unstable angina needing urgent revascularization (maximum duration: up to 3.3 years)
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Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
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Comparison groups |
Placebo v Bococizumab (PF-04950615)
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Number of subjects included in analysis |
16784
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.431903 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.82
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.49 | ||||||||||||
upper limit |
1.36 |
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End point title |
Event rate per 100 Subject-years For First Occurrence of Composite Endpoint of Cardiovascular Death, Non-Fatal Myocardial Infarction, Non-Fatal Stroke and Hospitalization for Unstable Angina | ||||||||||||
End point description |
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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
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End point type |
Secondary
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End point 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 3.3 years)
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Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
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Comparison groups |
Placebo v Bococizumab (PF-04950615)
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Number of subjects included in analysis |
16784
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.883797 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.98
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.8 | ||||||||||||
upper limit |
1.21 |
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End point title |
Event rate per 100 Subject-years For Cardiovascular Death | ||||||||||||
End point description |
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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
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End point type |
Secondary
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End point timeframe |
From baseline until the date of adjudicated and confirmed occurrence of cardiovascular death (maximum duration: up to 3.3 years)
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|
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Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
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Comparison groups |
Placebo v Bococizumab (PF-04950615)
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Number of subjects included in analysis |
16784
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.45569 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.74 | ||||||||||||
upper limit |
1.95 |
|
|||||||||||||
End point title |
Event rate per 100 Subject-years For First Occurrence of any Myocardial Infarction (Fatal or Non-Fatal) | ||||||||||||
End point description |
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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From baseline until the date of first adjudicated and confirmed occurrence of any MI (fatal or non-fatal) (maximum duration: up to 3.3 years)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
16784
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.469496 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.11
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.84 | ||||||||||||
upper limit |
1.48 |
|
|||||||||||||
End point title |
Event rate per 100 Subject-years For Fatal Myocardial Infarction | ||||||||||||
End point description |
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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From baseline until the date of adjudicated and confirmed occurrence of fatal MI (maximum duration: up to 3.3 years)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
16784
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.633022 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.54
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.26 | ||||||||||||
upper limit |
9.23 |
|
|||||||||||||
End point title |
Event rate per 100 Subject-years For First Occurrence of Non-Fatal Myocardial Infarction | ||||||||||||
End point description |
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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From baseline until the date of first adjudicated and confirmed occurrence of non-fatal MI (maximum duration: up to 3.3 years)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
16784
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.46765 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.11
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.83 | ||||||||||||
upper limit |
1.48 |
|
|||||||||||||
End point title |
Event rate per 100 Subject-years For First Occurrence of Any Stroke (Fatal or Non-Fatal) | ||||||||||||
End point description |
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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From baseline until the date of first adjudicated and confirmed occurrence of any stroke (fatal or non-fatal) (maximum duration: up to 3.3 years)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
16784
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.015462 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.53
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.32 | ||||||||||||
upper limit |
0.89 |
|
|||||||||||||
End point title |
Event rate per 100 Subject-years For First Occurrence of Any Stroke (Fatal or Non-Fatal), of Any Etiology | ||||||||||||
End point description |
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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point 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 3.3 years)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
16784
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.011863 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.54
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.33 | ||||||||||||
upper limit |
0.88 |
|
|||||||||||||
End point title |
Event rate per 100 Subject-years For Fatal Stroke | ||||||||||||
End point description |
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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From baseline until the date of first adjudicated and confirmed occurrence of fatal stroke (maximum duration: up to 3.3 years)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
16784
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.316066 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.12 | ||||||||||||
upper limit |
2 |
|
|||||||||||||
End point title |
Event rate per 100 Subject-years For First Occurrence of Non-Fatal Stroke | ||||||||||||
End point description |
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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From baseline until the date of first adjudicated and confirmed occurrence of non-fatal stroke (maximum duration: up to 3.3 years)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
16784
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.020328 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.52
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.3 | ||||||||||||
upper limit |
0.91 |
|
|||||||||||||
End point title |
Event rate per 100 Subject-years For First Occurrence of Hospitalization for Unstable Angina | ||||||||||||
End point description |
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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for unstable angina (maximum duration: up to 3.3 years)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
16784
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.367069 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.82
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.53 | ||||||||||||
upper limit |
1.27 |
|
|||||||||||||
End point title |
Event rate per 100 Subject-years For First Occurrence of Hospitalization for Congestive Heart Failure (CHF) | ||||||||||||
End point description |
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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From baseline until the date of first adjudicated and confirmed occurrence of hospitalization for congestive heart failure (maximum duration: up to 3.3 years)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
16784
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.443081 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.85
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.56 | ||||||||||||
upper limit |
1.29 |
|
|||||||||||||
End point title |
Event rate per 100 Subject-years For First Occurrence of Coronary Revascularization | ||||||||||||
End point description |
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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From baseline until the date of first adjudicated and confirmed occurrence of coronary revascularization (maximum duration: up to 3.3 years)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
16784
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.343817 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.9
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.71 | ||||||||||||
upper limit |
1.12 |
|
|||||||||||||
End point title |
Event rate per 100 Subject-years For First Occurrence of Coronary Artery Bypass Graft Surgery (CABG) | ||||||||||||
End point description |
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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From baseline until the date of first adjudicated and confirmed occurrence of CABG (maximum duration: up to 3.3 years)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
16784
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.889065 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.04
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.59 | ||||||||||||
upper limit |
1.85 |
|
|||||||||||||
End point title |
Event rate per 100 Subject-years For First Occurrence of Percutaneous Coronary Intervention (PCI) | ||||||||||||
End point description |
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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From baseline until the date of first adjudicated and confirmed occurrence of PCI (maximum duration: up to 3.3 years)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
16784
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.308388 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
0.88
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.69 | ||||||||||||
upper limit |
1.13 |
|
|||||||||||||
End point title |
Event rate per 100 Subject-years For First Occurrence of Any Arterial Revascularizations | ||||||||||||
End point description |
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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From baseline until the date of first adjudicated and confirmed occurrence of any arterial revascularizations (maximum duration: up to 3.3 years)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
16784
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.874835 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.03
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.74 | ||||||||||||
upper limit |
1.42 |
|
|||||||||||||
End point title |
Event rate per 100 Subject-years For All-Cause Death | ||||||||||||
End point description |
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 subject-years at risk. FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From baseline until the date of adjudicated and confirmed occurrence of all-cause death (maximum duration: up to 3.3 years)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Hazard ratio and 95% CI were from a Cox proportional hazards model stratified by geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL) with treatment as a covariate.
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
16784
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.526269 | ||||||||||||
Method |
Logrank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
1.12
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.79 | ||||||||||||
upper limit |
1.6 |
|
|||||||||||||
End point title |
Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Week 14 | ||||||||||||
End point description |
FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified. Here, "Number of subjects analyzed "(N) signifies those subjects who were evaluable for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 14
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
Lease Square (LS)- mean differences, associated 95% CI, and p-values were from a mixed model repeated measures (MMRM) model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
12887
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Mixed Effect Model Repeat Measurement | ||||||||||||
Parameter type |
LS-mean difference | ||||||||||||
Point estimate |
-60.57
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-61.43 | ||||||||||||
upper limit |
-59.71 |
|
|||||||||||||
End point title |
Nominal Change From Baseline in Low Density Lipoprotein Cholesterol at Week 14 | ||||||||||||
End point description |
FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified. Here, "N" signifies number of subjects who were evaluable for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 14
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
LS- mean differences and associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
12887
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Mixed Effect Model Repeat Measurement | ||||||||||||
Parameter type |
LS-mean difference | ||||||||||||
Point estimate |
-54.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-55.48 | ||||||||||||
upper limit |
-53.92 |
|
|||||||||||||
End point title |
Percent Change From Baseline in Low Density Lipoprotein Cholesterol at Last Post-Baseline Measurement | ||||||||||||
End point description |
FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified. Here, "N" signifies number of subjects who were evaluable for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, last post-baseline measurement (any time up to Week 140)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
LS- mean difference and associated 95% CI, and p-value were from an analysis of covariance (ANCOVA) model with fixed effects for treatment group, baseline value, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
16494
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
LS-mean difference | ||||||||||||
Point estimate |
-46.72
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-47.68 | ||||||||||||
upper limit |
-45.76 |
|
||||||||||||||||||||||||||||||||||
End point title |
Percent Change From Baseline in Lipid Levels at Week 14 | |||||||||||||||||||||||||||||||||
End point description |
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). FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified. Here, "n" signifies number of subjects who were evaluable at the specified categories for each arm respectively.
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Week 14
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | |||||||||||||||||||||||||||||||||
Statistical analysis description |
Non-HDL-C: LS- mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
16784
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||||||||
Method |
Mixed Effect Model Repeat Measurement | |||||||||||||||||||||||||||||||||
Parameter type |
LS-mean difference | |||||||||||||||||||||||||||||||||
Point estimate |
-54.88
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-55.66 | |||||||||||||||||||||||||||||||||
upper limit |
-54.09 | |||||||||||||||||||||||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | |||||||||||||||||||||||||||||||||
Statistical analysis description |
Total cholesterol: LS- mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
16784
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||||||||
Method |
Mixed Effect Model Repeat Measurement | |||||||||||||||||||||||||||||||||
Parameter type |
LS-mean difference | |||||||||||||||||||||||||||||||||
Point estimate |
-36.51
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-37.07 | |||||||||||||||||||||||||||||||||
upper limit |
-35.95 | |||||||||||||||||||||||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | |||||||||||||||||||||||||||||||||
Statistical analysis description |
VLDL-C: LS- mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
16784
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||||||||
Method |
Mixed Effect Model Repeat Measurement | |||||||||||||||||||||||||||||||||
Parameter type |
LS-mean difference | |||||||||||||||||||||||||||||||||
Point estimate |
-20.17
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-21.42 | |||||||||||||||||||||||||||||||||
upper limit |
-18.93 | |||||||||||||||||||||||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | |||||||||||||||||||||||||||||||||
Statistical analysis description |
RLP-C: LS- mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
16784
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||||||||
Method |
Mixed Effect Model Repeat Measurement | |||||||||||||||||||||||||||||||||
Parameter type |
LS-Mean Difference | |||||||||||||||||||||||||||||||||
Point estimate |
-30.25
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-32.44 | |||||||||||||||||||||||||||||||||
upper limit |
-28.07 | |||||||||||||||||||||||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | |||||||||||||||||||||||||||||||||
Statistical analysis description |
Apo B: LS -mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 52 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
16784
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||||||||
Method |
Mixed Effect Model Repeat Measurement | |||||||||||||||||||||||||||||||||
Parameter type |
LS-Mean Difference | |||||||||||||||||||||||||||||||||
Point estimate |
-58.55
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
-59.42 | |||||||||||||||||||||||||||||||||
upper limit |
-57.69 | |||||||||||||||||||||||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | |||||||||||||||||||||||||||||||||
Statistical analysis description |
HDL-C: LS- mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 70 with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
16784
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||||||||
Method |
Mixed Effect Model Repeat Measurement | |||||||||||||||||||||||||||||||||
Parameter type |
LS-Mean Difference | |||||||||||||||||||||||||||||||||
Point estimate |
6.14
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
5.69 | |||||||||||||||||||||||||||||||||
upper limit |
6.59 | |||||||||||||||||||||||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | |||||||||||||||||||||||||||||||||
Statistical analysis description |
Apo A-I: LS- mean differences, associated 95% CI, and p-values were from an MMRM model including observations through Week 52 with fixed effects for treatment group, visit,treatment group*visit interaction, baseline value, baseline value*visit interaction, geographic region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
|
|||||||||||||||||||||||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
|||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
16784
|
|||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||||||||
Method |
Mixed Effect Model Repeat Measurement | |||||||||||||||||||||||||||||||||
Parameter type |
LS-Mean Difference | |||||||||||||||||||||||||||||||||
Point estimate |
3.53
|
|||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||
lower limit |
3.02 | |||||||||||||||||||||||||||||||||
upper limit |
4.03 |
|
|||||||||||||||||||
End point title |
Percent Change From Baseline in Log-Transformed Lipoprotein (a) (Lp[a]) and Triglycerides at Week 14 | ||||||||||||||||||
End point description |
FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified. Here, "n" signifies number of subjects who were evaluable at the specified categories for each arm respectively.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Week 14
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||||||||
Statistical analysis description |
Lp (a): LS- mean differences and associated 95% CI, and p-values were from an MMRM model on the difference of log-transformed observations through Week 52 with fixed effects for treatment group, visit, treatment group*visit interaction, log-transformed baseline value, log-transformed baseline value*visit interaction, geographical region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
|
||||||||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||||||||
Number of subjects included in analysis |
16784
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||
Method |
Mixed Effect Model Repeat Measurement (M | ||||||||||||||||||
Parameter type |
LS-mean difference | ||||||||||||||||||
Point estimate |
0.67
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
0.66 | ||||||||||||||||||
upper limit |
0.68 | ||||||||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||||||||
Statistical analysis description |
Triglycerides: LS- mean differences and associated 95% CI, and p-values were from an MMRM model through Week 70 on the difference of log-transformed observations with fixed effects for treatment group, visit, treatment group*visit interaction, log-transformed baseline value, log-transformed baseline value*visit interaction, geographical region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
|
||||||||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||||||||
Number of subjects included in analysis |
16784
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||
Method |
Mixed Effect Model Repeat Measurement | ||||||||||||||||||
Parameter type |
LS-mean difference | ||||||||||||||||||
Point estimate |
0.81
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
0.8 | ||||||||||||||||||
upper limit |
0.81 |
|
|||||||||||||
End point title |
Percent Change From Baseline in Log-Transformed High Sensitivity C- Reactive Protein (hs-CRP) at Week 14 | ||||||||||||
End point description |
FAS: all subjects 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 subjects enrolled at study Site 3027 where a quality-related event was identified. Here, "N" signifies number of subjects who were evaluable for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 14
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Placebo vs PFÂ-04950615 150 mg | ||||||||||||
Statistical analysis description |
LS- mean differences and associated 95% CI, and p-values were from an MMRM model on the difference of log-transformed observations through Week 52 with fixed effects for treatment group, visit, treatment group*visit interaction, log-transformed baseline value, log-transformed baseline value*visit interaction, geographical region and LDL-C at pre-screening (<100 mg/dL, >=100 mg/dL).
|
||||||||||||
Comparison groups |
Placebo v Bococizumab (PF-04950615)
|
||||||||||||
Number of subjects included in analysis |
11861
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Mixed Effect Model Repeat Measurement | ||||||||||||
Parameter type |
LS-mean difference | ||||||||||||
Point estimate |
1.06
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
1.03 | ||||||||||||
upper limit |
1.1 |
|
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to 3.3 years
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Adverse event reporting additional description |
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
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
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Reporting groups
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Reporting group title |
Bococizumab (PF-04950615)
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Reporting group description |
Subjects received single dose of PF-04950615 150 milligrams, subcutaneous injection once in every 2 weeks over a period of 3.3 years. Subjects were followed up to 40 days after the last dose. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Subjects received single dose of placebo matched to PF-04950615 subcutaneous injection once in every 2 weeks over a period of 3.3 years. Subjects were followed up to 40 days after the last dose. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Notes [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [16] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [17] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [18] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [19] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [20] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [21] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [22] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [23] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [24] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [25] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. [26] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The event is gender specific event, hence number of subjects at risk are not equal to the total number of subjects. |
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Frequency threshold for reporting non-serious adverse events: 2% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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01 Oct 2014 |
1. An efficacy endpoint of any stroke (fatal and non-fatal), of any etiology which included hemorrhagic stroke, was added. 2. More frequent visits for assessment of direct LDL-C and AEs/serious AEs, for subjects who have had investigational product dose frequency modifications to quater 4 week so that the data monitoring committee can monitor more closely, lipid levels in subjects with a history of low levels of LDL-C during the trial was added. 3. Depression assessments was added so as to capture baseline risk for the disorder, given that depression was found fairly frequently in subjects at high risk of cardiovascular events and its presence might alter performance on the planned cognitive assessments. 4. Health care utilization assessments and endpoints was added to evaluate the potential impact of bococizumab on health care resource utilization. 5. Screening laboratory tests, hs-CRP and Lp(a) was added for subjects who had not had a prior cardiovascular event, since these were established risk factors for the occurrence of cardiovascular events. 6. Safety section was modified to clarify further, how serious adverse events were to be reported. |
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12 Feb 2016 |
1. Clinical secondary objectives and endpoints were updated to reflect an upgrading of the secondary endpoint of a composite endpoint of all-cause death, non-fatal MI and non-fatal stroke to a key secondary endpoint, in consideration of its clinical importance. The secondary endpoint of nominal change in hs-CRP was changed to percent change in hs-CRP. 2. The proposed indication was modified so that the major cardiovascular events reflected components of the primary endpoint. 3. The safety reporting section was revised to reflect the fact that a Pfizer internal serious adverse event triage group will ensure the correct reporting of serious AEs to the Pfizer Drug Safety Unit. 4. The cerebral hemorrhage risk exclusion was modified to clarify that a prior lacunar infarct refers to a prior lacunar stroke, ie, a lacunar infarct which resulted in a stroke. 5. An exclusion criterion of gastric bypass surgery was added, since its presence could complicate the interpretation of metabolic efficacy and safety data. 6. A requirement was added to the protocol that IP should not be administered, if a subject was prescribed a marketed proprotein convertase subtilisin/kexin type 9 inhibitor during the conduct of the study. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
As specified in SAP, due to discontinuation of the bococizumab clinical development program, health care resource utilization (HCRU) endpoints were not evaluated. |