Hypercholesterolemia
Conditions
Brief summary
Primary Objective: * To evaluate the effect of alirocumab (SAR236553/REGN727) on low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment in comparison with placebo in participants with LDL-C ≥ 100 mg/dL (≥ 2.59 mmol/L) on ongoing stable atorvastatin therapy. Secondary Objectives: * To evaluate the effects of alirocumab on other lipid levels after 12 weeks of treatment in comparison with placebo * To evaluate the safety and tolerability of alirocumab * To evaluate the development of anti-alirocumab antibodies * To evaluate the pharmacokinetics of alirocumab
Detailed description
The duration of study participation depended on the status of the participant at screening: * For participants receiving atorvastatin 10 mg, 20 mg, or 40 mg at a stable dose for at least 6 weeks prior to screening, the study participation was to be approximately 21 weeks including a screening period of 1 week, a double-blind treatment period of 12 weeks and a follow-up period of 8 weeks. * For participants receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening, or drug naive participants, the study participation was to be approximately 27 weeks including a screening period of 1 week, a run-in treatment period with atorvastatin 10 mg, 20 mg, or 40 mg at a stable dose of 6 weeks, a double-blind treatment period of 12 weeks, and a follow-up period of 8 weeks.
Interventions
DRUGAlirocumab
Two SC injections in the abdomen only.
Two subcutaneous (SC) injections in the abdomen only.
DRUGAtorvastatin
Orally once daily at a stable dose of 10 mg, 20 mg, or 40 mg as background therapy.
Sponsors
Regeneron Pharmaceuticals
Sanofi
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Participants with primary hypercholesterolemia receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening period or drug naive participants if they are likely to have low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥ 2.59 mmol/L) at the end of the 6-week run-in treatment period on atorvastatin therapy OR * Participants with primary hypercholesterolemia treated with atorvastatin at stable dose of 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to screening period and likely to have LDL-C ≥ 100 mg/dL (≥ 2.59 mmol/L) at the screening visit
Exclusion criteria
1. LDL-C \< 100 mg/dL (\< 2.59 mmol/L): * After the run-in period on atorvastatin (10 mg, 20 mg, or 40 mg) for participants receiving a lipid-lowering treatment other than atorvastatin or not at stable dose of atorvastatin 10 mg, 20 mg, or 40 mg for at least 6 weeks prior to the screening, or drug naive participant OR * At the first visit for participants who were being treated with stable dose of atorvastatin (10 mg, 20 mg, or 40 mg) for at least 6 weeks prior to screening 2. Participants not previously instructed on a cholesterol-lowering diet 3. Participants with type 1 diabetes 4. Participants with type 2 diabetes treated with insulin 5. Participants with type 2 diabetes and with an glycated hemoglobin (HbA1c) ≥ 8.5% at screening visit (considered poorly controlled) 6. Laboratory findings measured before randomization: * Triglycerides (TG) \> 350 mg/dL (\> 3.95 mmol/L) at screening visit * Positive serum or urine pregnancy test in females of childbearing potential 7. Pregnant or breast-feeding women 8. Women of childbearing potential with no effective contraceptive method The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | Baseline to Week 12 (LOCF) | Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first study drug injection up to 21 days after last study drug injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward \[LOCF\] method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis | Baseline to Week 12 (LOCF) | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. |
| Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis | Week 12 (LOCF) | — |
| Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis | Baseline to Week 12 (LOCF) | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. |
| Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis | Baseline to Week 12 (LOCF) | Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (inter-quartile range). |
| Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 12 - On-Treatment Analysis | Baseline to Week 12 (LOCF) | Adjusted LS mean and standard errors were estimated using the same ANCOVA as for primary endpoint. |
| Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Baseline to Week 12 (LOCF) | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 38 centers in the United States of America. Overall, 514 participants were screened between January 2011 and August 2011, 331 of whom were screen failures and screen failures were mainly due to exclusion criteria met.
Pre-assignment details
Randomization was stratified according to atorvastatin dose. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:1:1:1:1:1 ratio after confirmation of selection criteria. 183 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo (for alirocumab) Q2W for 12-weeks in combination with atorvastatin stable dose. | 31 |
| Alirocumab 50 mg Q2W Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose. | 30 |
| Alirocumab 100 mg Q2W Alirocumab 100 mg Q2W for 12-weeks in combination with atorvastatin stable dose. | 31 |
| Alirocumab 150 mg Q2W Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose. | 31 |
| Alirocumab 200 mg Q4W Alirocumab 200 mg Q4W and alternating placebo (for alirocumab) Q2W for 12-weeks in combination with atorvastatin stable dose. | 30 |
| Alirocumab 300 mg Q4W Alirocumab 300 mg Q4W and alternating placebo (for alirocumab) Q2W for 12-weeks in combination with atorvastatin stable dose. | 30 |
| Total | 183 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 1 | 3 | 1 |
| Overall Study | Consent withdrawn by Participant | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Other than above | 0 | 0 | 0 | 2 | 1 | 0 |
| Overall Study | Participant Moved | 0 | 0 | 0 | 1 | 2 | 1 |
| Overall Study | Poor compliance to protocol | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Study drug auto-injector administration | 0 | 0 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Alirocumab 50 mg Q2W | Alirocumab 100 mg Q2W | Alirocumab 150 mg Q2W | Alirocumab 200 mg Q4W | Alirocumab 300 mg Q4W | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 53.3 years STANDARD_DEVIATION 8.5 | 58.5 years STANDARD_DEVIATION 9.1 | 58.1 years STANDARD_DEVIATION 9.2 | 59.9 years STANDARD_DEVIATION 11.1 | 54.9 years STANDARD_DEVIATION 10.8 | 55.5 years STANDARD_DEVIATION 10.1 | 56.7 years STANDARD_DEVIATION 10 |
| LDL-C in mg/dL | 130.2 mg/dL STANDARD_DEVIATION 27.3 | 123.2 mg/dL STANDARD_DEVIATION 27.9 | 127.0 mg/dL STANDARD_DEVIATION 30.4 | 124.7 mg/dL STANDARD_DEVIATION 26.9 | 127.2 mg/dL STANDARD_DEVIATION 19.6 | 131.6 mg/dL STANDARD_DEVIATION 24.8 | 127.3 mg/dL STANDARD_DEVIATION 26.2 |
| Low-Density Lipoprotein Cholesterol (LDL-C) in mmol/L | 3.4 mmol/L STANDARD_DEVIATION 0.7 | 3.2 mmol/L STANDARD_DEVIATION 0.7 | 3.3 mmol/L STANDARD_DEVIATION 0.8 | 3.2 mmol/L STANDARD_DEVIATION 0.7 | 3.3 mmol/L STANDARD_DEVIATION 0.5 | 3.4 mmol/L STANDARD_DEVIATION 0.6 | 3.3 mmol/L STANDARD_DEVIATION 0.7 |
| Sex: Female, Male Female | 15 Participants | 13 Participants | 18 Participants | 21 Participants | 13 Participants | 16 Participants | 96 Participants |
| Sex: Female, Male Male | 16 Participants | 17 Participants | 13 Participants | 10 Participants | 17 Participants | 14 Participants | 87 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 | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 31 | 14 / 30 | 14 / 31 | 12 / 31 | 12 / 31 | 10 / 28 |
| serious Total, serious adverse events | 1 / 31 | 0 / 30 | 1 / 31 | 0 / 31 | 1 / 31 | 1 / 28 |
Outcome results
Primary
Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis
Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first study drug injection up to 21 days after last study drug injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward \[LOCF\] method.
Time frame: Baseline to Week 12 (LOCF)
Population: Modified Intent-To-Treat (mITT) population included all randomized participants with one baseline and at least one post baseline on-treatment calculated LDL-C.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -5.1 percent change | Standard Error 3.1 |
| Alirocumab 50 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -39.6 percent change | Standard Error 3.2 |
| Alirocumab 100 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -64.2 percent change | Standard Error 3.1 |
| Alirocumab 150 mg Q2W | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -72.4 percent change | Standard Error 3.2 |
| Alirocumab 200 mg Q4W | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -43.2 percent change | Standard Error 3.3 |
| Alirocumab 300 mg Q4W | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | -47.7 percent change | Standard Error 3.2 |
Comparison: Each treatment group was compared to placebo using ANCOVA-derived contrasts.~A hierarchical testing procedure was applied to ensure strong control of overall Type-I error rate at 0.05 level. Order was following:~1. Alirocumab 150 mg Q2W versus placebo~2. Alirocumab 300 mg Q4W versus placebo~3. Alirocumab 100 mg Q2W versus placebo~4. Alirocumab 200 mg Q4W versus placebo~5. Alirocumab 50 mg Q2W versus placebo~Testing continued only when high-order test was statistically significant at 5% levelp-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
p-value: <0.0001ANCOVA
Secondary
Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time frame: Baseline to Week 12 (LOCF)
Population: mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis | -7.6 mg/dL | Standard Error 3.9 |
| Alirocumab 50 mg Q2W | Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis | -53.0 mg/dL | Standard Error 4 |
| Alirocumab 100 mg Q2W | Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis | -81.2 mg/dL | Standard Error 3.9 |
| Alirocumab 150 mg Q2W | Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis | -92.0 mg/dL | Standard Error 4 |
| Alirocumab 200 mg Q4W | Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis | -56.4 mg/dL | Standard Error 4.1 |
| Alirocumab 300 mg Q4W | Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis | -62.5 mg/dL | Standard Error 4 |
Secondary
Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time frame: Baseline to Week 12 (LOCF)
Population: mITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis | -0.20 mmol/L | Standard Error 0.1 |
| Alirocumab 50 mg Q2W | Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis | -1.37 mmol/L | Standard Error 0.1 |
| Alirocumab 100 mg Q2W | Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis | -2.10 mmol/L | Standard Error 0.1 |
| Alirocumab 150 mg Q2W | Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis | -2.38 mmol/L | Standard Error 0.1 |
| Alirocumab 200 mg Q4W | Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis | -1.46 mmol/L | Standard Error 0.11 |
| Alirocumab 300 mg Q4W | Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis | -1.62 mmol/L | Standard Error 0.1 |
Secondary
Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 12 - On-Treatment Analysis
Adjusted LS mean and standard errors were estimated using the same ANCOVA as for primary endpoint.
Time frame: Baseline to Week 12 (LOCF)
Population: Participants of the mITT population with one baseline and at least one post-baseline on-treatment value for ApoB/ApoA-1 ratio analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 12 - On-Treatment Analysis | 0.05 ratio | Standard Error 0.03 |
| Alirocumab 50 mg Q2W | Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 12 - On-Treatment Analysis | -0.23 ratio | Standard Error 0.03 |
| Alirocumab 100 mg Q2W | Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 12 - On-Treatment Analysis | -0.35 ratio | Standard Error 0.03 |
| Alirocumab 150 mg Q2W | Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 12 - On-Treatment Analysis | -0.42 ratio | Standard Error 0.03 |
| Alirocumab 200 mg Q4W | Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 12 - On-Treatment Analysis | -0.23 ratio | Standard Error 0.03 |
| Alirocumab 300 mg Q4W | Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 12 - On-Treatment Analysis | -0.29 ratio | Standard Error 0.03 |
Secondary
Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis
Time frame: Week 12 (LOCF)
Population: mITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis | LDL-C <100 mg/dL (2.59 mmol/L) | 16.1 percentage of participants |
| Placebo | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis | LDL-C <70 mg/dL (1.81 mmol/L) | 3.2 percentage of participants |
| Alirocumab 50 mg Q2W | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis | LDL-C <100 mg/dL (2.59 mmol/L) | 93.3 percentage of participants |
| Alirocumab 50 mg Q2W | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis | LDL-C <70 mg/dL (1.81 mmol/L) | 46.7 percentage of participants |
| Alirocumab 100 mg Q2W | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis | LDL-C <100 mg/dL (2.59 mmol/L) | 96.8 percentage of participants |
| Alirocumab 100 mg Q2W | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis | LDL-C <70 mg/dL (1.81 mmol/L) | 83.9 percentage of participants |
| Alirocumab 150 mg Q2W | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis | LDL-C <100 mg/dL (2.59 mmol/L) | 100.0 percentage of participants |
| Alirocumab 150 mg Q2W | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis | LDL-C <70 mg/dL (1.81 mmol/L) | 100.0 percentage of participants |
| Alirocumab 200 mg Q4W | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis | LDL-C <100 mg/dL (2.59 mmol/L) | 89.3 percentage of participants |
| Alirocumab 200 mg Q4W | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis | LDL-C <70 mg/dL (1.81 mmol/L) | 46.4 percentage of participants |
| Alirocumab 300 mg Q4W | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis | LDL-C <100 mg/dL (2.59 mmol/L) | 96.7 percentage of participants |
| Alirocumab 300 mg Q4W | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and <70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis | LDL-C <70 mg/dL (1.81 mmol/L) | 56.7 percentage of participants |
Secondary
Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis
Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (inter-quartile range).
Time frame: Baseline to Week 12 (LOCF)
Population: Participants of the mITT population with one baseline and at least one post-baseline on-treatment value for lipid parameters analyzed. Here, n signifies number of participants analysed for each lipid parameter.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis | Fasting Triglycerides (n= 31, 30, 31, 29, 28, 30) | 9.7 percent change |
| Placebo | Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis | Lipoprotein(a) (n= 30, 30, 30, 29, 27, 30) | 0.0 percent change |
| Alirocumab 50 mg Q2W | Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis | Fasting Triglycerides (n= 31, 30, 31, 29, 28, 30) | -6.6 percent change |
| Alirocumab 50 mg Q2W | Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis | Lipoprotein(a) (n= 30, 30, 30, 29, 27, 30) | -13.3 percent change |
| Alirocumab 100 mg Q2W | Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis | Fasting Triglycerides (n= 31, 30, 31, 29, 28, 30) | -5.5 percent change |
| Alirocumab 100 mg Q2W | Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis | Lipoprotein(a) (n= 30, 30, 30, 29, 27, 30) | -26.1 percent change |
| Alirocumab 150 mg Q2W | Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis | Fasting Triglycerides (n= 31, 30, 31, 29, 28, 30) | -18.9 percent change |
| Alirocumab 150 mg Q2W | Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis | Lipoprotein(a) (n= 30, 30, 30, 29, 27, 30) | -28.6 percent change |
| Alirocumab 200 mg Q4W | Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis | Fasting Triglycerides (n= 31, 30, 31, 29, 28, 30) | -10.8 percent change |
| Alirocumab 200 mg Q4W | Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis | Lipoprotein(a) (n= 30, 30, 30, 29, 27, 30) | -16.7 percent change |
| Alirocumab 300 mg Q4W | Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis | Fasting Triglycerides (n= 31, 30, 31, 29, 28, 30) | -8.4 percent change |
| Alirocumab 300 mg Q4W | Percent Change From Baseline in Fasting Triglycerides and Lipoprotein(a) at Week 12 - On-Treatment Analysis | Lipoprotein(a) (n= 30, 30, 30, 29, 27, 30) | -7.9 percent change |
Secondary
Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis
Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint.
Time frame: Baseline to Week 12 (LOCF)
Population: Participants of the mITT population with one baseline and at least one post-baseline on-treatment value for lipid parameters analyzed. Here, n signifies the number of participants analysed for each lipid parameter.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Non-HDL-C (n= 31, 30, 31, 29, 28, 30) | -2.2 percent change | Standard Error 2.9 |
| Placebo | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Total Cholesterol (n= 31, 30, 31, 29, 28, 30) | -1.6 percent change | Standard Error 2.3 |
| Placebo | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Apo-B (n= 30, 30, 30, 29, 27, 30) | 2.2 percent change | Standard Error 2.9 |
| Placebo | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | HDL-C (n= 31, 30, 31, 29, 28, 30) | -1.0 percent change | Standard Error 2.3 |
| Alirocumab 50 mg Q2W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | HDL-C (n= 31, 30, 31, 29, 28, 30) | 6.7 percent change | Standard Error 2.4 |
| Alirocumab 50 mg Q2W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Apo-B (n= 30, 30, 30, 29, 27, 30) | -27.3 percent change | Standard Error 2.9 |
| Alirocumab 50 mg Q2W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Total Cholesterol (n= 31, 30, 31, 29, 28, 30) | -23.0 percent change | Standard Error 2.3 |
| Alirocumab 50 mg Q2W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Non-HDL-C (n= 31, 30, 31, 29, 28, 30) | -33.6 percent change | Standard Error 2.9 |
| Alirocumab 100 mg Q2W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Total Cholesterol (n= 31, 30, 31, 29, 28, 30) | -39.7 percent change | Standard Error 2.3 |
| Alirocumab 100 mg Q2W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | HDL-C (n= 31, 30, 31, 29, 28, 30) | 4.1 percent change | Standard Error 2.3 |
| Alirocumab 100 mg Q2W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Apo-B (n= 30, 30, 30, 29, 27, 30) | -48.1 percent change | Standard Error 2.9 |
| Alirocumab 100 mg Q2W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Non-HDL-C (n= 31, 30, 31, 29, 28, 30) | -55.6 percent change | Standard Error 2.9 |
| Alirocumab 150 mg Q2W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Total Cholesterol (n= 31, 30, 31, 29, 28, 30) | -45.2 percent change | Standard Error 2.3 |
| Alirocumab 150 mg Q2W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | HDL-C (n= 31, 30, 31, 29, 28, 30) | 5.5 percent change | Standard Error 2.4 |
| Alirocumab 150 mg Q2W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Non-HDL-C (n= 31, 30, 31, 29, 28, 30) | -62.5 percent change | Standard Error 3 |
| Alirocumab 150 mg Q2W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Apo-B (n= 30, 30, 30, 29, 27, 30) | -56.1 percent change | Standard Error 2.9 |
| Alirocumab 200 mg Q4W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | HDL-C (n= 31, 30, 31, 29, 28, 30) | 6.3 percent change | Standard Error 2.5 |
| Alirocumab 200 mg Q4W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Apo-B (n= 30, 30, 30, 29, 27, 30) | -28.7 percent change | Standard Error 3.1 |
| Alirocumab 200 mg Q4W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Non-HDL-C (n= 31, 30, 31, 29, 28, 30) | -37.4 percent change | Standard Error 3 |
| Alirocumab 200 mg Q4W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Total Cholesterol (n= 31, 30, 31, 29, 28, 30) | -28.0 percent change | Standard Error 2.4 |
| Alirocumab 300 mg Q4W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Total Cholesterol (n= 31, 30, 31, 29, 28, 30) | -29.8 percent change | Standard Error 2.3 |
| Alirocumab 300 mg Q4W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Apo-B (n= 30, 30, 30, 29, 27, 30) | -33.1 percent change | Standard Error 2.9 |
| Alirocumab 300 mg Q4W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | HDL-C (n= 31, 30, 31, 29, 28, 30) | 8.5 percent change | Standard Error 2.4 |
| Alirocumab 300 mg Q4W | Percent Change From Baseline in Total Cholesterol, High-density Lipoprotein Cholesterol (HDL-C), Non-HDL-C and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Non-HDL-C (n= 31, 30, 31, 29, 28, 30) | -40.7 percent change | Standard Error 2.9 |