Hyperlipidemia
Conditions
Keywords
mixed dyslipidemia, high risk of cardiovascular events, multiple cardiovascular disease risk factors
Brief summary
This study is a multicenter, randomized study in subjects with high cholesterol receiving highly effective statins to assess the efficacy, safety and tolerability of Bococizumab (PF-04950615;RN316) to lower LDL-C.
Interventions
150 mg every 2 weeks, subcutaneous injection, 12 months
OTHERPlacebo
subcutaneous injection every 2 weeks for 12 months
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Treated with a statin. * Fasting LDL-C \> 70 mg/dL and triglyceride \<=400 mg/dL. * High or very high risk of incurring a cardiovascular event.
Exclusion criteria
* Pregnant or breastfeeding females. * Cardiovascular or cerebrovascular event of procedures during the past 30 days. * Congestive heart failure NYHA class IV. * Poorly controlled hypertension.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | Baseline, Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52 | Baseline, Week 12, 24, 52 | — |
| Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Baseline, Week 12, 24, 52 | — |
| Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides (TG) Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Baseline, Week 12, 24, 52 | — |
| Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Baseline, Week 12, 24, 52 | — |
| Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12, 24 and 52 | Baseline, Week 12, 24, 52 | — |
| Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Baseline, Week 12, 24, 52 | — |
| Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24, 52: Treatment Period | Baseline, Week 24, 52 | — |
| Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52 | Baseline, Week 12, 24, 52 | — |
| Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Baseline, Week 12, 24, 52 | — |
| Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 | Baseline, Week 12, 24, 52 | — |
| Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52 | Baseline, Week 12, 24, 52 | — |
| Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12 | Baseline, Week 12 | — |
| Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12 | Baseline, Week 12 | — |
| Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | Baseline, Week 12 | — |
| Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52 | Baseline, Week 12, 24, 52 | — |
| Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12 | Baseline, Week 12 | — |
| Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12 | Baseline, Week 12 | — |
| Absolute Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12 | Baseline, Week 12 | — |
| Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12 | Baseline, Week 12 | — |
| Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Baseline, Week 12, 24, 52 | — |
| Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Baseline, Week 12, 24, 52 | — |
| Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 12, 24, 52 | — |
| Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 12, 24, 52 | — |
| Plasma Concentration of PF-04950615 at Week 12, 24 and 52 | Week 12, 24, 52 | Plasma concentration of PF-04950615 at Week 12, 24 and 52 was reported. |
| Number of Participants With Adverse Events (AEs) Related to Type 1 or 3 Hypersensitivity Reactions and Injection Site Reactions | Baseline up to Week 58 | Type 1 hypersensitivity or allergic reactions were possible in response to any injected protein and included shortness of breath, urticaria, anaphylaxis and angioedema. Type 3 hypersensitivity reactions were similar to Type 1 hypersensitivity reactions but were likely to be delayed from the time of injection and included symptoms such as rash, urticaria, polyarthritis, myalgia's, polysynovitis, fever and if severe then included glomerulonephritis. Injection site reactions included injection site bruising, discolouration, erythema, haematoma, haemorrhage, nodule, induration, inflammation, mass, pain, paraesthesia, pruritus, swelling, vesicles, warmth, scab and rash. Participants with type 1 or type 3 hypersensitivity reactions and participants with injection site reactions were reported in this outcome measure. |
| Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Treatment Period | Baseline up to Week 58 | Percentage of participants with at least 1 positive ADA titer or 1 positive nAb titer were reported. ADA titer \>=6.23 (log2) unit was considered to be ADA positive and nAb titer \>=1.58 (log2) unit was considered to be nAb positive. |
| Number of Participants Who Changed Concomitant Medication During Extension Period | Week 58 follow-up visit to Week 110 | In this outcome measure, total number of participants who changed their lipid-lowering medications or added a monoclonal antibody medication during the extension period were reported. |
| Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 Follow-up Visit, 71, 84, 97 and 110: Extension Period | Baseline, Week 58 follow-up visit, 71, 84, 97, 110 | — |
| Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 58 follow-up visit, Week 71, Week 84, Week 97, Week 110 | Percentage of participants with at least 1 positive ADA titer or 1 positive nAb titer were reported. ADA titer \>=6.23 (log2) unit was considered to be ADA positive and nAb titer \>=1.58 (log2) unit was considered to be nAb positive. |
| Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 | Baseline, Week 12 | — |
Countries
Canada, Colombia, France, Hungary, Lithuania, Mexico, Romania, Russia, Spain, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
This study was conducted at multiple sites from 28 October 2014 to 15 July 2016 for the Treatment Period and up to 10 July 2017 for the Extension Period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Treatment Period) Participants received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. | 1,071 |
| Bococizumab 150 mg (Treatment Period) Participants received Bococizumab (PF--04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52 and were followed up to Week 58. | 1,068 |
| Total | 2,139 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Extension Period | Withdrew Consent | 0 | 0 | 2 | 0 | 5 |
| Treatment Period | Adverse Event | 9 | 8 | 0 | 0 | 0 |
| Treatment Period | Death | 9 | 2 | 0 | 0 | 0 |
| Treatment Period | Did Not Meet Entrance Criteria | 2 | 3 | 0 | 0 | 0 |
| Treatment Period | Lost to Follow-up | 26 | 31 | 0 | 0 | 0 |
| Treatment Period | Other | 22 | 22 | 0 | 0 | 0 |
| Treatment Period | Protocol Violation | 1 | 2 | 0 | 0 | 0 |
| Treatment Period | Randomized Not Treated | 6 | 5 | 0 | 0 | 0 |
| Treatment Period | Withdrawal by Subject | 71 | 61 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo (Treatment Period) | Bococizumab 150 mg (Treatment Period) | Total |
|---|---|---|---|
| Age, Continuous | 62.2 years STANDARD_DEVIATION 9.8 | 61.8 years STANDARD_DEVIATION 9.3 | 62 years STANDARD_DEVIATION 9.6 |
| Sex: Female, Male Female | 434 Participants | 434 Participants | 868 Participants |
| Sex: Female, Male Male | 637 Participants | 634 Participants | 1271 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 1,065 | 2 / 1,063 | 0 / 47 | 0 / 19 | 0 / 39 |
| other Total, other adverse events | 138 / 1,065 | 177 / 1,063 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 150 / 1,065 | 116 / 1,063 | 1 / 47 | 1 / 19 | 1 / 39 |
Outcome results
Primary
Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
Time frame: Baseline, Week 12
Population: FAS included all participants who were randomized. Here, Number of participants analyzed (N) signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | 1.0 percent change | Standard Deviation 22.55 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -54.9 percent change | Standard Deviation 26.84 |
Comparison: Least square (LS) mean difference and associated 95 percent (%) confidence interval (CI), and p-value were derived from mixed effect model repeat measurement (MMRM) model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.p-value: <0.00195% CI: [-58.3, -54]MMRM
Secondary
Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12
Time frame: Baseline, Week 12
Population: FAS included all participants who were randomized. Here, n signifies number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12 | Change at Week 12 | -0.7 mg/dL | Standard Deviation 18.35 |
| Placebo (Treatment Period) | Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12 | Baseline | 94.0 mg/dL | Standard Deviation 24.26 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12 | Baseline | 92.3 mg/dL | Standard Deviation 22.74 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12 | Change at Week 12 | -46.0 mg/dL | Standard Deviation 26.58 |
Comparison: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-47.7, -43.9]
Secondary
Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12
Time frame: Baseline, Week 12
Population: FAS included all participants who were randomized. Here, n signifies number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12 | Baseline | 48.3 mg/dL | Standard Deviation 12.42 |
| Placebo (Treatment Period) | Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12 | Change at Week 12 | -0.1 mg/dL | Standard Deviation 6.84 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12 | Baseline | 47.8 mg/dL | Standard Deviation 12.72 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12 | Change at Week 12 | 2.5 mg/dL | Standard Deviation 7.07 |
Comparison: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [2.1, 3.3]
Secondary
Absolute Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12
Time frame: Baseline, Week 12
Population: FAS included all participants who were randomized. Here, n signifies number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Absolute Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12 | Baseline | 45.3 mg/dL | Standard Deviation 49.77 |
| Placebo (Treatment Period) | Absolute Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12 | Change at Week 12 | -0.0 mg/dL | Standard Deviation 12.07 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12 | Baseline | 46.4 mg/dL | Standard Deviation 55.57 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12 | Change at Week 12 | -10.6 mg/dL | Standard Deviation 18.36 |
Comparison: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-11.8, -9.3]
Secondary
Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
Time frame: Baseline, Week 12
Population: FAS included all participants who were randomized. Here, n signifies number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | Baseline | 113.5 mg/dL | Standard Deviation 35.9 |
| Placebo (Treatment Period) | Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | Change at Week 12 | -0.7 mg/dL | Standard Deviation 26.66 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | Baseline | 110.9 mg/dL | Standard Deviation 33.13 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | Change at Week 12 | -60.7 mg/dL | Standard Deviation 34.22 |
Comparison: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-63.5, -58.5]
Secondary
Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12
Time frame: Baseline, Week 12
Population: A subset of FAS included all participants who were randomized and had TG \>=200 mg/dL at pre-randomization. Here, n signifies number of participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12 | Baseline | 125.9 mg/dL | Standard Deviation 40.08 |
| Placebo (Treatment Period) | Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12 | Change at Week 12 | -3.4 mg/dL | Standard Deviation 29.08 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12 | Baseline | 121.5 mg/dL | Standard Deviation 37.84 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12 | Change at Week 12 | -64.8 mg/dL | Standard Deviation 38.94 |
Comparison: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction and geographical region. An unstructured variance covariance matrix was used.95% CI: [-68.3, -57.3]
Secondary
Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12
Time frame: Baseline, Week 12
Population: A subset of FAS included all participants who were randomized and had TG \<200 mg/dL at pre-randomization. Here, n signifies number of participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12 | Baseline | 109.1 mg/dL | Standard Deviation 33.24 |
| Placebo (Treatment Period) | Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12 | Change at Week 12 | 0.3 mg/dL | Standard Deviation 25.7 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12 | Baseline | 107.1 mg/dL | Standard Deviation 30.43 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12 | Change at Week 12 | -59.3 mg/dL | Standard Deviation 32.3 |
Comparison: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction and geographical region. An unstructured variance covariance matrix was used.95% CI: [-63.1, -57.6]
Secondary
Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12
Time frame: Baseline, Week 12
Population: FAS included all participants who were randomized. Here, n signifies number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12 | Baseline | 138.0 mg/dL | Standard Deviation 39.67 |
| Placebo (Treatment Period) | Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12 | Change at Week 12 | -1.6 mg/dL | Standard Deviation 30.93 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12 | Baseline | 135.3 mg/dL | Standard Deviation 36.85 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12 | Change at Week 12 | -67.0 mg/dL | Standard Deviation 38.89 |
Comparison: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-69.3, -63.6]
Secondary
Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12
Time frame: Baseline, Week 12
Population: FAS included all participants who were randomized. Here, n signifies number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 | Baseline | 186.3 mg/dL | Standard Deviation 40.77 |
| Placebo (Treatment Period) | Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 | Change at Week 12 | -1.8 mg/dL | Standard Deviation 31.62 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 | Baseline | 183.1 mg/dL | Standard Deviation 38.31 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 | Change at Week 12 | -64.5 mg/dL | Standard Deviation 38.01 |
Comparison: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-66.6, -60.9]
Secondary
Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52
Time frame: Baseline, Week 12, 24, 52
Population: FAS included all participants who were randomized. Here, n signifies number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Baseline | 4.1 Ratio | Standard Deviation 1.22 |
| Placebo (Treatment Period) | Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Change at Week 12 | -0.0 Ratio | Standard Deviation 0.86 |
| Placebo (Treatment Period) | Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Change at Week 24 | 0.0 Ratio | Standard Deviation 0.96 |
| Placebo (Treatment Period) | Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Change at Week 52 | -0.0 Ratio | Standard Deviation 0.97 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Change at Week 52 | -1.1 Ratio | Standard Deviation 1.21 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Baseline | 4.0 Ratio | Standard Deviation 1.19 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Change at Week 24 | -1.4 Ratio | Standard Deviation 1.15 |
| Bococizumab 150 mg (Treatment Period) | Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Change at Week 12 | -1.5 Ratio | Standard Deviation 1.09 |
Comparison: Week 12: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-1.6, -1.5]
Comparison: Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-1.5, -1.3]
Comparison: Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-1.2, -1]
Secondary
Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52
Time frame: Baseline, Week 12, 24, 52
Population: FAS included all participants who were randomized. Here, n signifies number of participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Baseline | 0.7 Ratio | Standard Deviation 0.21 |
| Placebo (Treatment Period) | Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Change at Week 12 | 0.0 Ratio | Standard Deviation 0.14 |
| Placebo (Treatment Period) | Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Change at Week 24 | 0.0 Ratio | Standard Deviation 0.15 |
| Placebo (Treatment Period) | Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Change at Week 52 | 0.0 Ratio | Standard Deviation 0.16 |
| Bococizumab 150 mg (Treatment Period) | Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Change at Week 52 | -0.2 Ratio | Standard Deviation 0.23 |
| Bococizumab 150 mg (Treatment Period) | Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Baseline | 0.7 Ratio | Standard Deviation 0.2 |
| Bococizumab 150 mg (Treatment Period) | Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Change at Week 24 | -0.3 Ratio | Standard Deviation 0.23 |
| Bococizumab 150 mg (Treatment Period) | Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Change at Week 12 | -0.3 Ratio | Standard Deviation 0.21 |
Comparison: Week 12: LS mean difference and associated 95% confidence interval CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-0.3, -0.3]
Comparison: Week 24: LS mean difference and associated 95% confidence interval CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-0.3, -0.3]
Comparison: Week 52: LS mean difference and associated 95% confidence interval CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-0.3, -0.2]
Secondary
Number of Participants Who Changed Concomitant Medication During Extension Period
In this outcome measure, total number of participants who changed their lipid-lowering medications or added a monoclonal antibody medication during the extension period were reported.
Time frame: Week 58 follow-up visit to Week 110
Population: All participants who consented for extension period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Treatment Period) | Number of Participants Who Changed Concomitant Medication During Extension Period | 2 Participants |
| Bococizumab 150 mg (Treatment Period) | Number of Participants Who Changed Concomitant Medication During Extension Period | 1 Participants |
| Bococizumab ADA Negative (Extension Period) | Number of Participants Who Changed Concomitant Medication During Extension Period | 2 Participants |
Secondary
Number of Participants With Adverse Events (AEs) Related to Type 1 or 3 Hypersensitivity Reactions and Injection Site Reactions
Type 1 hypersensitivity or allergic reactions were possible in response to any injected protein and included shortness of breath, urticaria, anaphylaxis and angioedema. Type 3 hypersensitivity reactions were similar to Type 1 hypersensitivity reactions but were likely to be delayed from the time of injection and included symptoms such as rash, urticaria, polyarthritis, myalgia's, polysynovitis, fever and if severe then included glomerulonephritis. Injection site reactions included injection site bruising, discolouration, erythema, haematoma, haemorrhage, nodule, induration, inflammation, mass, pain, paraesthesia, pruritus, swelling, vesicles, warmth, scab and rash. Participants with type 1 or type 3 hypersensitivity reactions and participants with injection site reactions were reported in this outcome measure.
Time frame: Baseline up to Week 58
Population: Safety analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Treatment Period) | Number of Participants With Adverse Events (AEs) Related to Type 1 or 3 Hypersensitivity Reactions and Injection Site Reactions | Type 1 or 3 hypersensitivity reactions | 2 Participants |
| Placebo (Treatment Period) | Number of Participants With Adverse Events (AEs) Related to Type 1 or 3 Hypersensitivity Reactions and Injection Site Reactions | Injection site reactions | 56 Participants |
| Bococizumab 150 mg (Treatment Period) | Number of Participants With Adverse Events (AEs) Related to Type 1 or 3 Hypersensitivity Reactions and Injection Site Reactions | Type 1 or 3 hypersensitivity reactions | 2 Participants |
| Bococizumab 150 mg (Treatment Period) | Number of Participants With Adverse Events (AEs) Related to Type 1 or 3 Hypersensitivity Reactions and Injection Site Reactions | Injection site reactions | 144 Participants |
Secondary
Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52
Time frame: Week 12, 24, 52
Population: FAS included all participants who were randomized. Here, 'n' signifies those participants who were evaluable at specified time points for each arm respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Treatment Period) | Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 12 | 45.3 percentage of participants |
| Placebo (Treatment Period) | Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 2 | 43.2 percentage of participants |
| Placebo (Treatment Period) | Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 52 | 45.0 percentage of participants |
| Bococizumab 150 mg (Treatment Period) | Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 12 | 90.9 percentage of participants |
| Bococizumab 150 mg (Treatment Period) | Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 2 | 85.8 percentage of participants |
| Bococizumab 150 mg (Treatment Period) | Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 52 | 79.8 percentage of participants |
Comparison: Week 12: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.95% CI: [19.21, 38.02]
Comparison: Week 24: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.95% CI: [9.84, 16.86]
Comparison: Week 52: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.95% CI: [4.99, 8.06]
Secondary
Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52
Time frame: Week 12, 24, 52
Population: FAS included all participants who were randomized. Here, 'n' signifies those participants who were evaluable at specified time points for each arm respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Treatment Period) | Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 12 | 5.9 percentage of participants |
| Placebo (Treatment Period) | Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 24 | 7.8 percentage of participants |
| Placebo (Treatment Period) | Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 52 | 6.8 percentage of participants |
| Bococizumab 150 mg (Treatment Period) | Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 12 | 78.6 percentage of participants |
| Bococizumab 150 mg (Treatment Period) | Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 24 | 69.8 percentage of participants |
| Bococizumab 150 mg (Treatment Period) | Percentage of Participants Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 52 | 61.4 percentage of participants |
Comparison: Week 12: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.95% CI: [61.74, 121.25]
Comparison: Week 24: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.95% CI: [26.83, 47.96]
Comparison: Week 52: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.95% CI: [18.9, 34.47]
Secondary
Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period
Percentage of participants with at least 1 positive ADA titer or 1 positive nAb titer were reported. ADA titer \>=6.23 (log2) unit was considered to be ADA positive and nAb titer \>=1.58 (log2) unit was considered to be nAb positive.
Time frame: Week 58 follow-up visit, Week 71, Week 84, Week 97, Week 110
Population: All participants who consented for extension period. This outcome measure was planned not to be analyzed for reporting arms Placebo (Extension period) and Bococizumab ADA negative (Extension period). Here, n signifies number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Treatment Period) | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 58 follow-up visit: ADA | 100.0 Percentage of participants |
| Placebo (Treatment Period) | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 58 follow-up visit: nAB | 36.8 Percentage of participants |
| Placebo (Treatment Period) | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 71: ADA | 62.5 Percentage of participants |
| Placebo (Treatment Period) | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 71: nAB | 31.3 Percentage of participants |
| Placebo (Treatment Period) | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 84: ADA | 81.8 Percentage of participants |
| Placebo (Treatment Period) | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 84: nAB | 45.5 Percentage of participants |
| Placebo (Treatment Period) | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 97: ADA | 50.0 Percentage of participants |
| Placebo (Treatment Period) | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 97: nAB | 0.0 Percentage of participants |
| Placebo (Treatment Period) | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 110: ADA | 85.7 Percentage of participants |
| Placebo (Treatment Period) | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 110: nAB | 57.1 Percentage of participants |
Secondary
Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Treatment Period
Percentage of participants with at least 1 positive ADA titer or 1 positive nAb titer were reported. ADA titer \>=6.23 (log2) unit was considered to be ADA positive and nAb titer \>=1.58 (log2) unit was considered to be nAb positive.
Time frame: Baseline up to Week 58
Population: Safety analysis population included all participants who received at least 1 dose of study treatment. Here, N signifies those participants who were evaluable for this outcome measure for each reporting arm respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Treatment Period) | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Treatment Period | Baseline up to Week 58: ADA | 0.9 Percentage of participants |
| Placebo (Treatment Period) | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Treatment Period | Baseline up to Week 58: nAb | 0.4 Percentage of participants |
| Bococizumab 150 mg (Treatment Period) | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Treatment Period | Baseline up to Week 58: ADA | 46.7 Percentage of participants |
| Bococizumab 150 mg (Treatment Period) | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Treatment Period | Baseline up to Week 58: nAb | 30.3 Percentage of participants |
Secondary
Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52
Time frame: Baseline, Week 12, 24, 52
Population: FAS included all participants who were randomized. Here, n signifies number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Week 12 | -0.6 percent change | Standard Deviation 11.22 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Week 24 | -0.9 percent change | Standard Deviation 12.1 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Week 52 | -1.2 percent change | Standard Deviation 12.34 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Week 12 | 2.8 percent change | Standard Deviation 11.73 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Week 24 | 2.7 percent change | Standard Deviation 11.93 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Week 52 | 2.6 percent change | Standard Deviation 13.75 |
Comparison: Week 12: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [2.4, 4.3]
Comparison: Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [2.5, 4.5]
Comparison: Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [2.7, 4.9]
Secondary
Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52
Time frame: Baseline, Week 12, 24, 52
Population: FAS included all participants who were randomized. Here, n signifies number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 | Week 12 | -1.2 percent change | Standard Deviation 13.05 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 | Week 24 | -0.9 percent change | Standard Deviation 13.56 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 | Week 52 | -2.5 percent change | Standard Deviation 13.5 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 | Week 12 | -1.0 percent change | Standard Deviation 13.75 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 | Week 24 | 0.1 percent change | Standard Deviation 14.28 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 | Week 52 | -1.0 percent change | Standard Deviation 13.72 |
Comparison: Week 12: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-0.9, 1.4]
Comparison: Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-0.1, 2.3]
Comparison: Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [0.3, 2.7]
Secondary
Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52
Time frame: Baseline, Week 12, 24, 52
Population: FAS included all participants who were randomized. Here, n signifies number of participants who were evaluable at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52 | Week 12 | 0.4 percent change | Standard Deviation 18.83 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52 | Week 24 | 1.5 percent change | Standard Deviation 21.43 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52 | Week 52 | -0.4 percent change | Standard Deviation 21.78 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52 | Week 12 | -50.4 percent change | Standard Deviation 27.42 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52 | Week 24 | -44.9 percent change | Standard Deviation 31.17 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52 | Week 52 | -37.4 percent change | Standard Deviation 32.92 |
Comparison: Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.p-value: <0.00195% CI: [-52.9, -48.8]MMRM
Comparison: Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-48.5, -43.8]
Comparison: Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-38.6, -33.6]
Secondary
Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52
Time frame: Baseline, Week 12, 24, 52
Population: FAS included all participants who were randomized. Here, n signifies number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 12 | 0.4 percent change | Standard Deviation 13.92 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 24 | 0.5 percent change | Standard Deviation 15.25 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 52 | 1.2 percent change | Standard Deviation 16.09 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 12 | 6.2 percent change | Standard Deviation 14.99 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 24 | 6.1 percent change | Standard Deviation 15.32 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 52 | 6.5 percent change | Standard Deviation 17.87 |
Comparison: Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.p-value: <0.00195% CI: [4.5, 7]MMRM
Comparison: Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [4.2, 6.8]
Comparison: Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [3.7, 6.7]
Secondary
Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12, 24 and 52
Time frame: Baseline, Week 12, 24, 52
Population: FAS included all participants who were randomized. Here, n signifies number of participants who were evaluable at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12, 24 and 52 | Week 12 | 2.4 percent change | Standard Deviation 85.08 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12, 24 and 52 | Week 24 | 8.7 percent change | Standard Deviation 146 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12, 24 and 52 | Week 52 | 4.3 percent change | Standard Deviation 139.49 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12, 24 and 52 | Week 12 | -26.3 percent change | Standard Deviation 42.63 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12, 24 and 52 | Week 24 | -22.7 percent change | Standard Deviation 51.48 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Lipoprotein (a) (Lp[a]) at Week 12, 24 and 52 | Week 52 | -20.9 percent change | Standard Deviation 110.14 |
Comparison: Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.p-value: <0.00195% CI: [-34.4, -22.5]MMRM
Comparison: Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-40.6, -21.5]
Comparison: Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-36.8, -13.7]
Secondary
Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24, 52: Treatment Period
Time frame: Baseline, Week 24, 52
Population: FAS included all participants who were randomized. Here, N signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24, 52: Treatment Period | Week 24 | 3.2 percent change | Standard Deviation 27.45 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24, 52: Treatment Period | Week 52 | 2.1 percent change | Standard Deviation 27 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24, 52: Treatment Period | Week 24 | -47.5 percent change | Standard Deviation 32.5 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24, 52: Treatment Period | Week 52 | -39.5 percent change | Standard Deviation 36.08 |
Comparison: Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-53.3, -48]
Comparison: Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-43.5, -37.8]
Secondary
Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 Follow-up Visit, 71, 84, 97 and 110: Extension Period
Time frame: Baseline, Week 58 follow-up visit, 71, 84, 97, 110
Population: All participants who consented for extension period. This outcome measure was planned not to be analyzed for reporting arms: Placebo (Extension Period) and Bococizumab ADA negative (Extension Period). Here, n signifies number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 Follow-up Visit, 71, 84, 97 and 110: Extension Period | Week 58 follow-up visit | -6.4 percent change | Standard Deviation 24.67 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 Follow-up Visit, 71, 84, 97 and 110: Extension Period | Week 71 | -10.4 percent change | Standard Deviation 41.51 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 Follow-up Visit, 71, 84, 97 and 110: Extension Period | Week 84 | -15.8 percent change | Standard Deviation 25.65 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 Follow-up Visit, 71, 84, 97 and 110: Extension Period | Week 97 | -20.8 percent change | Standard Deviation 31.08 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 Follow-up Visit, 71, 84, 97 and 110: Extension Period | Week 110 | -5.0 percent change | Standard Deviation 28.65 |
Secondary
Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52
Time frame: Baseline, Week 12, 24, 52
Population: A subset of FAS included all participants who were randomized and had TG \>=200 mg/dL at pre-randomization. Here, n signifies number of participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 12 | -1.5 percent change | Standard Deviation 20.82 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 24 | 1.1 percent change | Standard Deviation 28.21 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 52 | -1.2 percent change | Standard Deviation 27.78 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 12 | -53.0 percent change | Standard Deviation 26.9 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 24 | -42.8 percent change | Standard Deviation 31.87 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 52 | -36.3 percent change | Standard Deviation 34.88 |
Comparison: Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction and geographical region. An unstructured variance covariance matrix was used.p-value: <0.00195% CI: [-55.9, -47.7]MMRM
Comparison: Week 24: LS mean difference and associated 95% CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction and geographical region. An unstructured variance covariance matrix was used.95% CI: [-49.1, -38.8]
Comparison: Week 52: LS mean difference and associated 95% CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction and geographical region. An unstructured variance covariance matrix was used.95% CI: [-40.2, -29]
Secondary
Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides (TG) Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52
Time frame: Baseline, Week 12, 24, 52
Population: A subset of FAS included all participants who were randomized and had TG \<200 mg/dL at pre-randomization. Here, n signifies number of participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides (TG) Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 12 | 1.9 percent change | Standard Deviation 23.07 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides (TG) Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 24 | 3.9 percent change | Standard Deviation 27.17 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides (TG) Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 52 | 3.2 percent change | Standard Deviation 26.65 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides (TG) Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 12 | -55.6 percent change | Standard Deviation 26.81 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides (TG) Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 24 | -49.2 percent change | Standard Deviation 32.58 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides (TG) Cut-off of Less Than (<) 200 Milligram Per Deciliter (mg/dL) at Week 12, 24 and 52 | Week 52 | -40.6 percent change | Standard Deviation 36.45 |
Comparison: Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction and geographical region. An unstructured variance covariance matrix was used.p-value: <0.00195% CI: [-60.2, -55.2]MMRM
Comparison: Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction and geographical region. An unstructured variance covariance matrix was used.95% CI: [-56.1, -50]
Comparison: Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction and geographical region. An unstructured variance covariance matrix was used.95% CI: [-46.2, -39.5]
Secondary
Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52
Time frame: Baseline, Week 12, 24, 52
Population: FAS included all participants who were randomized. Here, n signifies number of participants who were evaluable at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 12 | 0.2 percent change | Standard Deviation 21.22 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 24 | 1.6 percent change | Standard Deviation 24.65 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 52 | -0.3 percent change | Standard Deviation 24.62 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 12 | -49.7 percent change | Standard Deviation 25.51 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 24 | -43.8 percent change | Standard Deviation 30.02 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 52 | -36.8 percent change | Standard Deviation 32.73 |
Comparison: Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.p-value: <0.00195% CI: [-52.1, -48]MMRM
Comparison: Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-47.9, -43.1]
Comparison: Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-38.5, -33.3]
Secondary
Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52
Time frame: Baseline, Week 12, 24, 52
Population: FAS included all participants who were randomized. Here, n signifies number of participants who were evaluable at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52 | Week 12 | -0.1 percent change | Standard Deviation 16.18 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52 | Week 24 | 1.0 percent change | Standard Deviation 18.68 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52 | Week 52 | -0.3 percent change | Standard Deviation 18.75 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52 | Week 12 | -34.9 percent change | Standard Deviation 18.34 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52 | Week 24 | -30.5 percent change | Standard Deviation 21.56 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52 | Week 52 | -25.3 percent change | Standard Deviation 23.43 |
Comparison: Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.p-value: <0.00195% CI: [-36.5, -33.5]MMRM
Comparison: Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-33.3, -29.8]
Comparison: Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-26.6, -22.8]
Secondary
Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52
Time frame: Baseline, Week 12, 24, 52
Population: FAS included all participants who were randomized. Here, n signifies number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52 | Week 12 | 3.5 percent change | Standard Deviation 38.25 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52 | Week 24 | 5.1 percent change | Standard Deviation 51.06 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52 | Week 52 | 0.3 percent change | Standard Deviation 43.63 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52 | Week 12 | -12.9 percent change | Standard Deviation 39.99 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52 | Week 24 | -11.5 percent change | Standard Deviation 41.33 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52 | Week 52 | -12.5 percent change | Standard Deviation 40.82 |
Comparison: Week 12: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-20, -13.2]
Comparison: Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-20.7, -12.6]
Comparison: Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-16.5, -9]
Secondary
Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52
Time frame: Baseline, Week 12, 24, 52
Population: FAS included all participants who were randomized. Here, n signifies number of participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52 | Week 12 | 3.5 percent change | Standard Deviation 38.25 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52 | Week 24 | 5.1 percent change | Standard Deviation 51.06 |
| Placebo (Treatment Period) | Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52 | Week 52 | 0.3 percent change | Standard Deviation 43.63 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52 | Week 12 | -12.9 percent change | Standard Deviation 39.99 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52 | Week 24 | -11.5 percent change | Standard Deviation 41.33 |
| Bococizumab 150 mg (Treatment Period) | Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52 | Week 52 | -12.5 percent change | Standard Deviation 40.82 |
Comparison: Week 12: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-20, -13.2]
Comparison: Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-20.7, -12.6]
Comparison: Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group\*visit interaction, baseline value, baseline value\*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-16.5, -9]
Secondary
Plasma Concentration of PF-04950615 at Week 12, 24 and 52
Plasma concentration of PF-04950615 at Week 12, 24 and 52 was reported.
Time frame: Week 12, 24, 52
Population: Analysis set included participants who received at least 1 dose of PF-04950615. Here, n signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Treatment Period) | Plasma Concentration of PF-04950615 at Week 12, 24 and 52 | Week 12 | 4.91 Microgram per milliliter | Standard Deviation 4.987 |
| Placebo (Treatment Period) | Plasma Concentration of PF-04950615 at Week 12, 24 and 52 | Week 24 | 4.74 Microgram per milliliter | Standard Deviation 5.772 |
| Placebo (Treatment Period) | Plasma Concentration of PF-04950615 at Week 12, 24 and 52 | Week 52 | 3.60 Microgram per milliliter | Standard Deviation 4.685 |