Hyperlipidemia
Conditions
Keywords
Primary hyperlipidemia or mixed dyslipidemia, high risk of cardiovascular events, multiple cardiovascular disease risk factors.
Brief summary
This study is a multicenter, double-blind, randomized study to access the efficacy, safety and tolerability of Bococizumab (PF-04950615; RN316) in subjects with hyperlipidemia receiving background statin therapy.
Interventions
150 mg every 2 weeks, subcutaneous injection for 52 weeks.
OTHERPlacebo
Subcutaneous injection every 2 weeks for 52 weeks.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Treated with a statin * Fasting LDL-C \>=100 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 or procedure within 90 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 (Non 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 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 (Non 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 | — |
| Absolute 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 Versus Time Summary of PF-04950615 | Week 12, 24, 52 | — |
| Percentage of Participants With Adverse Events (AEs) Related to Type 1 and 3 Hypersensitivity Reactions and Injection Site Reactions | Baseline up to end of study (up to 110 weeks) | 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 (log 2) unit was considered to be ADA positive and nAb titer \>=1.58 (log 2) unit was considered to be nAb positive. |
| Number of Participants Who Changed Concomitant Medication During Extension Period | Week 58 follow-up 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), 71, 84, 97 and 110: Extension Period | Baseline, Week 58 (follow up), 71, 84, 97, 110 | — |
| Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 58 (follow-up), 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, Czechia, Finland, Netherlands, Norway, Poland, Puerto Rico, Singapore, South Korea, Sweden, 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 |
|---|---|
| Treatment Period: Placebo 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. | 247 |
| Treatment Period: Bococizumab 150 mg Participants received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Participants were followed up to Week 58. | 499 |
| Total | 746 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Extension Period | Withdrew consent | 0 | 0 | 2 | 0 | 0 |
| Treatment Period | Adverse Event | 0 | 5 | 0 | 0 | 0 |
| Treatment Period | Death | 2 | 2 | 0 | 0 | 0 |
| Treatment Period | Did Not Meet Entrance Criteria | 0 | 1 | 0 | 0 | 0 |
| Treatment Period | Lost to Follow-up | 5 | 17 | 0 | 0 | 0 |
| Treatment Period | Other | 9 | 11 | 0 | 0 | 0 |
| Treatment Period | Protocol Violation | 1 | 1 | 0 | 0 | 0 |
| Treatment Period | Withdrawal by Subject | 12 | 37 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Treatment Period: Placebo | Treatment Period: Bococizumab 150 mg | Total |
|---|---|---|---|
| Age, Continuous | 61.7 years STANDARD_DEVIATION 10 | 61.5 years STANDARD_DEVIATION 9.9 | 61.6 years STANDARD_DEVIATION 9.9 |
| Sex: Female, Male Female | 107 Participants | 223 Participants | 330 Participants |
| Sex: Female, Male Male | 140 Participants | 276 Participants | 416 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 | 2 / 247 | 2 / 499 | 0 / 44 | 0 / 33 | 0 / 56 |
| other Total, other adverse events | 29 / 247 | 97 / 499 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 32 / 247 | 44 / 499 | 2 / 44 | 0 / 33 | 1 / 56 |
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 |
|---|---|---|---|
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -0.8 percent change | Standard Deviation 17.61 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -50.8 percent change | Standard Deviation 29.81 |
Comparison: Least square (LS) mean difference and associated 95% confidence interval (CI), and p-value were derived from an 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: [-54, -45.8]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 |
|---|---|---|---|---|
| Treatment Period: Placebo | Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12 | Baseline | 106.1 mg/dL | Standard Deviation 20.43 |
| Treatment Period: Placebo | Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12 | Change at Week 12 | -1.6 mg/dL | Standard Deviation 18.09 |
| Treatment Period: Bococizumab 150 mg | Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12 | Baseline | 107.1 mg/dL | Standard Deviation 23.33 |
| Treatment Period: Bococizumab 150 mg | Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12 | Change at Week 12 | -49.8 mg/dL | Standard Deviation 31.81 |
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: [-51.9, -43.6]
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 |
|---|---|---|---|---|
| Treatment Period: Placebo | Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12 | Baseline | 49.2 mg/dL | Standard Deviation 13.2 |
| Treatment Period: Placebo | 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 6.75 |
| Treatment Period: Bococizumab 150 mg | Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12 | Baseline | 48.3 mg/dL | Standard Deviation 11.6 |
| Treatment Period: Bococizumab 150 mg | 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 6.64 |
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: [1.6, 3.6]
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 |
|---|---|---|---|---|
| Treatment Period: Placebo | Absolute Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12 | Baseline | 48.5 mg/dL | Standard Deviation 54.04 |
| Treatment Period: Placebo | Absolute Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12 | Change at Week 12 | 0.1 mg/dL | Standard Deviation 10.91 |
| Treatment Period: Bococizumab 150 mg | Absolute Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12 | Baseline | 47.3 mg/dL | Standard Deviation 53.55 |
| Treatment Period: Bococizumab 150 mg | Absolute Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12 | Change at Week 12 | -10.3 mg/dL | Standard Deviation 17.01 |
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: [-12.5, -8.3]
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 |
|---|---|---|---|---|
| Treatment Period: Placebo | Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | Baseline | 134.7 mg/dL | Standard Deviation 29.71 |
| Treatment Period: Placebo | Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | Change at Week 12 | -2.5 mg/dL | Standard Deviation 25.07 |
| Treatment Period: Bococizumab 150 mg | Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | Baseline | 135.9 mg/dL | Standard Deviation 33.67 |
| Treatment Period: Bococizumab 150 mg | Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | Change at Week 12 | -69.6 mg/dL | Standard Deviation 42.98 |
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: [-72, -61.1]
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 |
|---|---|---|---|---|
| Treatment Period: Placebo | 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 | 143.7 mg/dL | Standard Deviation 35.49 |
| Treatment Period: Placebo | 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 | -6.6 mg/dL | Standard Deviation 29.61 |
| Treatment Period: Bococizumab 150 mg | 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 | 147.2 mg/dL | Standard Deviation 39.48 |
| Treatment Period: Bococizumab 150 mg | 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 | -74.1 mg/dL | Standard Deviation 48.04 |
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: [-76.7, -55.4]
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 |
|---|---|---|---|---|
| Treatment Period: Placebo | 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 | 130.1 mg/dL | Standard Deviation 25.22 |
| Treatment Period: Placebo | 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 | -0.5 mg/dL | Standard Deviation 22.37 |
| Treatment Period: Bococizumab 150 mg | 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 | 130.2 mg/dL | Standard Deviation 28.72 |
| Treatment Period: Bococizumab 150 mg | 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 | -67.3 mg/dL | Standard Deviation 40.14 |
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: [-73, -60.5]
Secondary
Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non 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 |
|---|---|---|---|---|
| Treatment Period: Placebo | Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12 | Change at Week 12 | -5.8 mg/dL | Standard Deviation 29.59 |
| Treatment Period: Placebo | Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12 | Baseline | 160.2 mg/dL | Standard Deviation 33.49 |
| Treatment Period: Bococizumab 150 mg | Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12 | Change at Week 12 | -77.9 mg/dL | Standard Deviation 48.28 |
| Treatment Period: Bococizumab 150 mg | Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12 | Baseline | 162.1 mg/dL | Standard Deviation 37.78 |
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: [-77.5, -65.1]
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 |
|---|---|---|---|---|
| Treatment Period: Placebo | Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 | Baseline | 209.4 mg/dL | Standard Deviation 33.84 |
| Treatment Period: Placebo | Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 | Change at Week 12 | -5.9 mg/dL | Standard Deviation 29.61 |
| Treatment Period: Bococizumab 150 mg | Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 | Baseline | 210.3 mg/dL | Standard Deviation 37.97 |
| Treatment Period: Bococizumab 150 mg | Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12 | Change at Week 12 | -75.4 mg/dL | Standard Deviation 46.91 |
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: [-75.2, -63.1]
Secondary
Absolute 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 |
|---|---|---|---|---|
| Treatment Period: Placebo | Absolute 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 |
| Treatment Period: Placebo | Absolute 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 0.66 |
| Treatment Period: Placebo | Absolute 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 0.16 |
| Treatment Period: Placebo | Absolute 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 0.25 |
| Treatment Period: Bococizumab 150 mg | Absolute 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 0.27 |
| Treatment Period: Bococizumab 150 mg | Absolute 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 | -0.4 ratio | Standard Deviation 0.25 |
| Treatment Period: Bococizumab 150 mg | Absolute Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Baseline | 0.8 ratio | Standard Deviation 0.22 |
| Treatment Period: Bococizumab 150 mg | Absolute 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 | -0.3 ratio | Standard Deviation 0.25 |
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: [-0.4, -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: [-0.4, -0.2]
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 |
|---|---|---|---|---|
| Treatment Period: Placebo | 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 | 4.6 ratio | Standard Deviation 1.9 |
| Treatment Period: Placebo | 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 | -0.2 ratio | Standard Deviation 1.27 |
| Treatment Period: Placebo | 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 | -0.2 ratio | Standard Deviation 1.42 |
| Treatment Period: Placebo | 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 | -0.2 ratio | Standard Deviation 1.62 |
| Treatment Period: Bococizumab 150 mg | 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 | -1.5 ratio | Standard Deviation 1.32 |
| Treatment Period: Bococizumab 150 mg | 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 | 4.6 ratio | Standard Deviation 1.31 |
| Treatment Period: Bococizumab 150 mg | 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 | -1.6 ratio | Standard Deviation 1.38 |
| Treatment Period: Bococizumab 150 mg | 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 | -1.8 ratio | Standard Deviation 1.29 |
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: [-1.8, -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: [-1.6, -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: [-1.6, -1.2]
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 to Week 110
Population: All participants who consented for extension period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Period: Placebo | Number of Participants Who Changed Concomitant Medication During Extension Period | 2 Participants |
| Treatment Period: Bococizumab 150 mg | Number of Participants Who Changed Concomitant Medication During Extension Period | 4 Participants |
| Extension Period: Bococizumab ADA Negative | Number of Participants Who Changed Concomitant Medication During Extension Period | 3 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) |
|---|---|---|---|
| Treatment Period: Placebo | 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 | 10.2 percentage of participants |
| Treatment Period: Placebo | 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 24 | 19.9 percentage of participants |
| Treatment Period: Placebo | 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 | 25.2 percentage of participants |
| Treatment Period: Bococizumab 150 mg | 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 | 81.6 percentage of participants |
| Treatment Period: Bococizumab 150 mg | 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 24 | 75.1 percentage of participants |
| Treatment Period: Bococizumab 150 mg | 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 | 72.7 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: [32.08, 90.59]
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: [11.15, 26.07]
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: [6.18, 13.48]
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) |
|---|---|---|---|
| Treatment Period: Placebo | 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 | 1.3 percentage of participants |
| Treatment Period: Placebo | 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 | 1.7 percentage of participants |
| Treatment Period: Placebo | 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 | 3.2 percentage of participants |
| Treatment Period: Bococizumab 150 mg | 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 | 62.2 percentage of participants |
| Treatment Period: Bococizumab 150 mg | 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 | 60.1 percentage of participants |
| Treatment Period: Bococizumab 150 mg | 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 | 53.4 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: [48.84, 501.11]
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: [39.77, 308.46]
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: [19.52, 96.13]
Secondary
Percentage of Participants With Adverse Events (AEs) Related to Type 1 and 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 end of study (up to 110 weeks)
Population: Safety analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Period: Placebo | Percentage of Participants With Adverse Events (AEs) Related to Type 1 and 3 Hypersensitivity Reactions and Injection Site Reactions | With type 1 or 3 hypersensitivity reactions | 0.0 Percentage of participants |
| Treatment Period: Placebo | Percentage of Participants With Adverse Events (AEs) Related to Type 1 and 3 Hypersensitivity Reactions and Injection Site Reactions | With injection site reactions | 0.8 Percentage of participants |
| Treatment Period: Bococizumab 150 mg | Percentage of Participants With Adverse Events (AEs) Related to Type 1 and 3 Hypersensitivity Reactions and Injection Site Reactions | With type 1 or 3 hypersensitivity reactions | 0.2 Percentage of participants |
| Treatment Period: Bococizumab 150 mg | Percentage of Participants With Adverse Events (AEs) Related to Type 1 and 3 Hypersensitivity Reactions and Injection Site Reactions | With injection site reactions | 13.4 Percentage of participants |
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), 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) |
|---|---|---|---|
| Treatment Period: Placebo | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 58 (follow up): ADA positive | 100.0 percentage of participants |
| Treatment Period: Placebo | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 58 (follow up): nAB positive | 60.6 percentage of participants |
| Treatment Period: Placebo | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 71: ADA positive | 87.1 percentage of participants |
| Treatment Period: Placebo | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 71: nAB positive | 35.5 percentage of participants |
| Treatment Period: Placebo | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 84: ADA positive | 82.1 percentage of participants |
| Treatment Period: Placebo | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 84: nAB positive | 25.0 percentage of participants |
| Treatment Period: Placebo | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 97: ADA positive | 86.4 percentage of participants |
| Treatment Period: Placebo | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 97: nAB positive | 18.2 percentage of participants |
| Treatment Period: Placebo | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 110: ADA positive | 100.0 percentage of participants |
| Treatment Period: Placebo | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period | Week 110: nAB positive | 11.8 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 (log 2) unit was considered to be ADA positive and nAb titer \>=1.58 (log 2) unit was considered to be nAb positive.
Time frame: Baseline up to Week 58
Population: Analysis set included all participants who received at least 1 dose of PF-04950615 150 mg. This outcome measure was planned not to be analysed for placebo reporting arm. Here N signifies number of subjects who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Period: Placebo | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Treatment Period | Baseline up to Week 58: ADA positive | 54.8 Percentage of participants |
| Treatment Period: Placebo | Percentage of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Treatment Period | Baseline up to Week 58: nAb positive | 37.9 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 |
|---|---|---|---|---|
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Week 12 | -0.9 percent change | Standard Deviation 11.09 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Week 24 | -1.6 percent change | Standard Deviation 10.81 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Week 52 | -1.0 percent change | Standard Deviation 13.12 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Week 12 | 3.4 percent change | Standard Deviation 11.43 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Week 24 | 2.5 percent change | Standard Deviation 11.61 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52 | Week 52 | 3.4 percent change | Standard Deviation 11.77 |
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: [2.5, 5.8]
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: [2.2, 5.5]
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: [2.4, 6.2]
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 |
|---|---|---|---|---|
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 | Week 12 | 2.0 percent change | Standard Deviation 11.94 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 | Week 24 | 2.6 percent change | Standard Deviation 12.12 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 | Week 52 | 0.7 percent change | Standard Deviation 12.46 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 | Week 12 | 3.0 percent change | Standard Deviation 11.94 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 | Week 24 | 3.7 percent change | Standard Deviation 14.12 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52 | Week 52 | 1.9 percent change | Standard Deviation 12.22 |
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: [-0.7, 2.8]
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: [-1.1, 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, 2.7]
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 |
|---|---|---|---|---|
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52 | Week 12 | -0.6 percent change | Standard Deviation 16.7 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52 | Week 24 | -2.1 percent change | Standard Deviation 18.66 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52 | Week 52 | -4.4 percent change | Standard Deviation 20.77 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52 | Week 12 | -46.5 percent change | Standard Deviation 28.87 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52 | Week 24 | -43.5 percent change | Standard Deviation 32.26 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52 | Week 52 | -37.3 percent change | Standard Deviation 29.59 |
Comparison: Week 12: LS mean difference and associated 95% CI, and p-value 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.p-value: <0.00195% CI: [-49.7, -41.7]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, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-45.3, -36.5]
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, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-36.7, -28.2]
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 |
|---|---|---|---|---|
| Treatment Period: Placebo | Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 12 | 0.6 percent change | Standard Deviation 13.93 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 24 | 0.6 percent change | Standard Deviation 14.88 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 52 | 0.7 percent change | Standard Deviation 14.24 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 12 | 6.3 percent change | Standard Deviation 13.86 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 24 | 6.3 percent change | Standard Deviation 14.49 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52 | Week 52 | 7.0 percent change | Standard Deviation 15.6 |
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: [3.4, 7.6]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: [3.2, 7.6]
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: [3.6, 8.3]
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 |
|---|---|---|---|---|
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12, 24 and 52 | Week 12 | 4.9 percent change | Standard Deviation 54.24 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12, 24 and 52 | Week 24 | 5.9 percent change | Standard Deviation 50.52 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12, 24 and 52 | Week 52 | 27.9 percent change | Standard Deviation 374.64 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12, 24 and 52 | Week 12 | -25.7 percent change | Standard Deviation 29.45 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12, 24 and 52 | Week 24 | -21.3 percent change | Standard Deviation 34.42 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12, 24 and 52 | Week 52 | -21.5 percent change | Standard Deviation 32.61 |
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: [-36.9, -24.6]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: [-33.9, -21.2]
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: [-85.2, -13.5]
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 at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24, 52: Treatment Period | Week 24 | -2.9 percent change | Standard Deviation 21.72 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24, 52: Treatment Period | Week 52 | -4.7 percent change | Standard Deviation 23.96 |
| Treatment Period: Bococizumab 150 mg | 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 33.48 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24, 52: Treatment Period | Week 52 | -41.8 percent change | Standard Deviation 32.67 |
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: [-48.8, -39.5]
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: [-40.9, -31.4]
Secondary
Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 (Follow up), 71, 84, 97 and 110: Extension Period
Time frame: Baseline, Week 58 (follow up), 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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 (Follow up), 71, 84, 97 and 110: Extension Period | Week 58 (follow up) | 6.7 percent change | Standard Deviation 27.7 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 (Follow up), 71, 84, 97 and 110: Extension Period | Week 71 | 8.7 percent change | Standard Deviation 34.83 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 (Follow up), 71, 84, 97 and 110: Extension Period | Week 84 | 7.0 percent change | Standard Deviation 30.34 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 (Follow up), 71, 84, 97 and 110: Extension Period | Week 97 | 2.6 percent change | Standard Deviation 31.43 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 (Follow up), 71, 84, 97 and 110: Extension Period | Week 110 | 15.5 percent change | Standard Deviation 36.17 |
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 |
|---|---|---|---|---|
| Treatment Period: Placebo | 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 | -5.7 percent change | Standard Deviation 21.67 |
| Treatment Period: Placebo | 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 | -5.7 percent change | Standard Deviation 23.78 |
| Treatment Period: Bococizumab 150 mg | 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 | -45.8 percent change | Standard Deviation 33.13 |
| Treatment Period: Bococizumab 150 mg | 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 | -40.9 percent change | Standard Deviation 30.25 |
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: [-53.7, -39.5]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: [-47.9, -31.6]
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: [-41.3, -25.5]
Secondary
Percent 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, 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 who were evaluable at the specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Period: Placebo | Percent 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, 24 and 52 | Week 12 | 0.5 percent change | Standard Deviation 16.61 |
| Treatment Period: Placebo | Percent 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, 24 and 52 | Week 24 | -1.6 percent change | Standard Deviation 21.68 |
| Treatment Period: Placebo | Percent 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, 24 and 52 | Week 52 | -4.2 percent change | Standard Deviation 24.11 |
| Treatment Period: Bococizumab 150 mg | Percent 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, 24 and 52 | Week 12 | -51.1 percent change | Standard Deviation 30.43 |
| Treatment Period: Bococizumab 150 mg | Percent 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, 24 and 52 | Week 24 | -48.4 percent change | Standard Deviation 33.67 |
| Treatment Period: Bococizumab 150 mg | Percent 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, 24 and 52 | Week 52 | -42.2 percent change | Standard Deviation 33.75 |
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: [-56.7, -46.6]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: [-52.2, -40.6]
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 and geographical region. An unstructured variance covariance matrix was used.95% CI: [-43.3, -31.4]
Secondary
Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non 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 |
|---|---|---|---|---|
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12, 24 and 52 | Week 12 | -2.6 percent change | Standard Deviation 17.57 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12, 24 and 52 | Week 24 | -3.8 percent change | Standard Deviation 20.63 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12, 24 and 52 | Week 52 | -6.4 percent change | Standard Deviation 22.7 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12, 24 and 52 | Week 12 | -47.6 percent change | Standard Deviation 28.36 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12, 24 and 52 | Week 24 | -44.7 percent change | Standard Deviation 30.83 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non HDL-C) at Week 12, 24 and 52 | Week 52 | -39.5 percent change | Standard Deviation 29.36 |
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: [-48.9, -41.1]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: [-44.8, -36.1]
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: [-37, -28.4]
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 |
|---|---|---|---|---|
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52 | Week 12 | -2.2 percent change | Standard Deviation 13.41 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52 | Week 24 | -3.1 percent change | Standard Deviation 15.79 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52 | Week 52 | -5.0 percent change | Standard Deviation 17.22 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52 | Week 12 | -35.4 percent change | Standard Deviation 20.93 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52 | Week 24 | -32.9 percent change | Standard Deviation 23.06 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52 | Week 52 | -29.0 percent change | Standard Deviation 22.08 |
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: [-36.1, -30.2]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, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-32.8, -26.3]
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, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.95% CI: [-27, -20.5]
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 |
|---|---|---|---|---|
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52 | Week 12 | -6.2 percent change | Standard Deviation 32.92 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52 | Week 24 | -8.9 percent change | Standard Deviation 35.6 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52 | Week 52 | -8.0 percent change | Standard Deviation 41.46 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52 | Week 12 | -16.2 percent change | Standard Deviation 32.86 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52 | Week 24 | -18.2 percent change | Standard Deviation 65.13 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52 | Week 52 | -15.8 percent change | Standard Deviation 35.57 |
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: [-15.1, -5.1]
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: [-17.9, -0.2]
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: [-14.1, -2.2]
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 |
|---|---|---|---|---|
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52 | Week 12 | -6.2 percent change | Standard Deviation 32.92 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52 | Week 24 | -8.9 percent change | Standard Deviation 35.6 |
| Treatment Period: Placebo | Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52 | Week 52 | -8.0 percent change | Standard Deviation 41.46 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52 | Week 12 | -16.2 percent change | Standard Deviation 32.86 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52 | Week 24 | -18.2 percent change | Standard Deviation 65.13 |
| Treatment Period: Bococizumab 150 mg | Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52 | Week 52 | -15.8 percent change | Standard Deviation 35.57 |
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: [-15.1, -5.1]
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: [-17.9, -0.2]
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: [-14.1, -2.2]
Secondary
Plasma Concentration Versus Time Summary of PF-04950615
Time frame: Week 12, 24, 52
Population: Analysis set included participants who received at least 1 dose of PF-04950615. This outcome measure was planned not to be analysed for placebo reporting arm. Here, n signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Period: Placebo | Plasma Concentration Versus Time Summary of PF-04950615 | Week 12 | 5.37 microgram per milliliter | Standard Deviation 5.327 |
| Treatment Period: Placebo | Plasma Concentration Versus Time Summary of PF-04950615 | Week 24 | 5.28 microgram per milliliter | Standard Deviation 5.888 |
| Treatment Period: Placebo | Plasma Concentration Versus Time Summary of PF-04950615 | Week 52 | 4.01 microgram per milliliter | Standard Deviation 4.652 |