Hypercholesterolemia
Conditions
Brief summary
Primary Objective: To provide participants with severe hypercholesterolemia at risk for subsequent cardiovascular (CV) events and not adequately controlled with currently available lipid-modifying therapy (LMT) access to alirocumab ahead of commercial availability and to document the overall safety and tolerability of alirocumab in this participant population. Secondary Objectives: To document the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels as well as non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (total-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels after 12 weeks of treatment. To document participant's acceptability of self-injection (Self Injection Assessment Questionnaire, SIAQ).
Detailed description
The study duration included a screening period of up to 3 weeks, a treatment period of a minimum of 12 weeks and up to a maximum of 120 weeks (30 months), and at least 2 weeks after the last study treatment injection.
Interventions
Pharmaceutical form:solution Route of administration: subcutaneous
DRUGplacebo (for injection training only)
Pharmaceutical form:solution Route of administration: subcutaneous
DRUGezetimibe
Pharmaceutical form:capsule Route of administration: oral
DRUGatorvastatin
Pharmaceutical form:tablet Route of administration: oral
DRUGrosuvastatin
Pharmaceutical form:tablet Route of administration: oral
DRUGsimvastatin
Pharmaceutical form:tablet Route of administration: oral
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Either A, B, C, D, or E below and not adequately controlled with a maximally tolerated dose of statin with or without other LMTs, all at stable doses for at least 4 weeks prior to the screening visit (Week-3): A. Participants suffering from heterozygous familial hypercholesterolemia (heFH) with LDL-C concentrations greater than or equal to (\>=)160 mg/dL (4.14 millimoles per liter \[mmol/L\]) despite treatment. B. Participants suffering from heFH with LDL-C concentrations \>=130 mg/dL (3.36 mmol/L) despite treatment and two or more CV risk factors among this list: * LDL-C greater than (\>) 250 milligrams per deciliter (mg/dL) (6.46 mmol/L) at the time of the familial hypercholesterolemia (FH) diagnosis (before treatment). * Family history of premature-onset coronary heart disease (CHD; first-degree male relative with onset before age 55 years; first-degree female relative with onset before age 65 years). * Metabolic syndrome. * HDL-C less than (\<) 40 mg/dL (1.03 mmol/L). * Hypertension (blood pressure \>140/90 mmHg or drug treatment). * Lipoprotein a (Lp\[a\]) \>=50 mg/dL (1.78 µmol/L). * Tendon xanthoma. C. Participants suffering from heFH with LDL-C concentrations \>=130 mg/dL (3.36 mmol/L) despite treatment and one of the following characteristics: * Established CHD or other cardiovascular disease (CVD; history of acute myocardial infarction, ischemic stroke, peripheral arterial disease, coronary or peripheral arterial revascularization, stable or unstable angina, transient ischemic attack, carotid artery stenosis \>=50 percent (%), or aortic abdominal aneurysm). * Drug-treated type 2 diabetes mellitus or type 1 with target organ damage. * Family history of first- or second-degree relative with very premature onset CHD (first- or second-degree male relative with onset before age 45; first- or second-degree female relative with onset before age 55). D. Non-FH participants suffering from established CHD or other CVD (history of acute myocardial infarction (MI), ischemic stroke, peripheral arterial disease, coronary or peripheral arterial revascularization, stable or unstable angina, transient ischemic attack, carotid artery stenosis \>=50%, or aortic abdominal aneurysm) and with LDL-C concentrations \>=130 mg/dL (3.36 mmol/L). E. Participants suffering from progressive CVD (coronary artery disease, or peripheral arterial occlusive disease or cerebrovascular disease as documented clinically or by imaging techniques, with a subsequent CV event \[acute MI, ischemic stroke, ischemia-driven revascularization, unstable angina, transient ischemic attack\] occurring despite stable doses of maximally tolerated LMT) with LDL-C concentrations \>=100 mg/dL (2.59 mmol/L).
Exclusion criteria
Not on a stable dose of LMT (including statin) for at least 4 weeks prior to the screening visit (Week -3) and from screening to enrollment. Use of a fibrate other than fenofibrate within 4 weeks of the screening visit (Week-3) or between screening and enrollment. Daily doses above atorvastatin 80 mg, rosuvastatin 40 mg, or simvastatin 40 mg (except for participants on simvastatin 80 mg for more than one year, who were eligible). Use of statin other than simvastatin, atorvastatin, or rosuvastatin prior to the screening visit (Week-3) or between screening and enrollment, except when there was a documented reason for intolerance to the above mentioned potent statins (in which case the use of a different statin was allowed). Fasting serum TG \>400 mg/dL (\>4.52 mmol/L) at the screening visit (Week -3). Uncontrolled hypertension (\>180 mmHg systolic and/or \>110 mmHg diastolic at randomization visit). New York Heart Association Class III or IV congestive heart failure persisting despite treatment. History of hemorrhagic stroke. Liver transaminases \>3 times the upper limit of normal. Laboratory evidence of current hepatitis B or C infection. Creatine kinase \>3 times the upper limit of normal. Estimated glomerular filtration rate \<30 mL/min/1.73 m\^2. Pregnant or breastfeeding woman or with childbearing potential without appropriate contraception. Male participant with a female partner of childbearing potential not protected by a highly-effective method(s) of birth control. Participants eligible for enrollment into an ongoing clinical study of alirocumab conducted at the same investigational site. Hypersensitivity to alirocumab or any of the excipients. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | From first injection of investigational medicinal product (IMP) up to 2 weeks after last dose of study drug (Week 120) | Adverse Event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Treatment-emergent AEs (TEAEs) were defined as AEs that that developed or worsened or became serious during the TEAE period (time from the first injection of study drug up to the day of the last injection of study drug + 14 days). A Serious Adverse Event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 | At Week 12 | LDL-Cholesterol was calculated using the Friedewald formula. Percentage of participants who reached calculated LDL-C \<100 mg/dL (2.59 mmol/L) at week 12 were reported. |
| Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 12 | At Week 12 | LDL-Cholesterol was calculated using the Friedewald formula. Percentage of participants who reached calculated LDL-C \<70 mg/dL (1.81 mmol/L) at week 12 were reported. |
| Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) and/or >=50% Reduction From Baseline in LDL-C at Week 12 | At Week 12 | LDL-Cholesterol was calculated using the Friedewald formula. Percentage of participants who reached LDL-C \<70 mg/dL at Week 12 and/or \>=50% reduction from baseline in LDL-C at Week 12 are reported. |
| Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 | Baseline, Week 12 | Baseline value was defined as the last observation before the first dose of the treatment. |
| Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | Baseline, Week 12 | Calculated LDL-C values were obtained using the Friedewald formula. Calculated LDL-C in mg/dL from Friedewald formula (LDL cholesterol = Total cholesterol - HDL cholesterol - \[Triglyceride/5\]). Baseline value was defined as the last observation before the first dose of the treatment. |
| Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12 | Baseline, Week 12 | Baseline value was defined as the last observation before the first dose of the treatment. |
| Percent Change From Baseline in Triglycerides at Week 12 | Baseline, Week 12 | Baseline value was defined as the last observation before the first dose of the treatment. |
| Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Baseline (Pre-SIAQ), Week 4, Week 8, Week 12, Week 24, Week 48, Week 72, Week 96 | Pre-SIAQ: self-completed before first self-injection & Post-SIAQ: self-completed after self-injection. Pre-SIAQ consisted of 7 items grouped into 3 domains:feelings about injections,self-confidence & satisfaction with self-injection. Post-SIAQ consisted of 21 items grouped into 6 domains:feelings about injections,self-image,self-confidence,injection-site reactions,ease of use & satisfaction with self-injection. Participants rated each item on 5-point (or 6-point) semantic Likert-type scale, where lower numbers indicate a worse experience. Item scores were transformed to obtain a score ranging from 0 (worst experience) to 10 (best experience). Transformed scores for items contributing to a domain were then averaged into a domain score. Each domain score ranges from 0 (worst experience) to 10 (best experience), higher score=better acceptability. Domain scores common to the Pre & Post SIAQ were analyzed on participants belonging to Pre & Post-SIAQ population and are reported. |
| Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Week 4, Week 8, Week 12, Week 24, Week 48, Week 72, Week 96 | SIAQ: contained 2 modules: Pre-SIAQ and Post-SIAQ. Post-SIAQ: self-completed after self-injection. Post-SIAQ consisted of 21 items grouped into 6 domains: feelings about injections, self-image, self-confidence, injection-site reactions, ease of use & satisfaction with self-injection. Participants rated each item on 5-point (or 6-point) semantic Likert-type scale, where lower numbers indicated a worse experience. Item scores were transformed to obtain a score ranging from 0 (worst experience) to 10 (best experience) for each item. Transformed scores for items contributing to a domain were then averaged into a domain score. Each domain score ranges from 0 (worst experience) to 10 (best experience), higher score=better acceptability. Domain scores which are not in common with Pre-SIAQ were analyzed on the Post-SIAQ population and are reported here. |
| Percent Change From Baseline in Total Cholesterol (Total-C) at Week 12 | Baseline, Week 12 | Baseline value was defined as the last observation before the first dose of the treatment. |
Countries
Austria, Belgium, Canada, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, Poland, Romania, Slovakia, Slovenia, Spain, Switzerland
Participant flow
Recruitment details
The study was conducted at 156 sites in 17 countries. A total of 1305 participants were screened between 23-June-2015 to 27-December 2016, of whom 307 were screen failures. Screen failures were mainly due to exclusion criteria met.
Pre-assignment details
A total of 998 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Alirocumab Participants received Alirocumab 150 mg SC Q2W or 75 mg SC Q2W added to stable LMT up to a maximum of 120 weeks. Alirocumab dose was either up-titrated from 75 to 150 mg Q2W or down-titrated from 150 to 75 mg Q2W, based on Investigator judgment and treatment response. | 994 |
| Total | 994 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 41 |
| Overall Study | Death | 4 |
| Overall Study | Enrolled but not treated | 4 |
| Overall Study | Excluded from study | 1 |
| Overall Study | Lack of treatment efficacy | 2 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Participant did not wish to continue | 39 |
| Overall Study | Physician Decision | 5 |
| Overall Study | Poor compliance to study protocol | 3 |
| Overall Study | Pregnancy | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Sponsor decision | 6 |
| Overall Study | Study ended treatment not available | 4 |
| Overall Study | Switched to commercial drug | 4 |
Baseline characteristics
| Characteristic | Alirocumab |
|---|---|
| Age, Continuous | 56.6 years STANDARD_DEVIATION 11.7 |
| Race/Ethnicity, Customized Asian/Oriental | 6 Participants |
| Race/Ethnicity, Customized Black | 10 Participants |
| Race/Ethnicity, Customized Multiracial | 1 Participants |
| Race/Ethnicity, Customized Other | 8 Participants |
| Race/Ethnicity, Customized White/Caucasian | 969 Participants |
| Sex: Female, Male Female | 369 Participants |
| Sex: Female, Male Male | 625 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 994 |
| other Total, other adverse events | 221 / 994 |
| serious Total, serious adverse events | 161 / 994 |
Outcome results
Primary
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
Adverse Event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Treatment-emergent AEs (TEAEs) were defined as AEs that that developed or worsened or became serious during the TEAE period (time from the first injection of study drug up to the day of the last injection of study drug + 14 days). A Serious Adverse Event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.
Time frame: From first injection of investigational medicinal product (IMP) up to 2 weeks after last dose of study drug (Week 120)
Population: Analysis was performed on safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alirocumab | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE | 71.6 percentage of participants |
| Alirocumab | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | Any treatment emergent SAE | 16.2 percentage of participants |
| Alirocumab | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to death | 0.2 percentage of participants |
| Alirocumab | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | Any TEAE leading to treatment discontinuation | 4.5 percentage of participants |
Secondary
Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections
Pre-SIAQ: self-completed before first self-injection & Post-SIAQ: self-completed after self-injection. Pre-SIAQ consisted of 7 items grouped into 3 domains:feelings about injections,self-confidence & satisfaction with self-injection. Post-SIAQ consisted of 21 items grouped into 6 domains:feelings about injections,self-image,self-confidence,injection-site reactions,ease of use & satisfaction with self-injection. Participants rated each item on 5-point (or 6-point) semantic Likert-type scale, where lower numbers indicate a worse experience. Item scores were transformed to obtain a score ranging from 0 (worst experience) to 10 (best experience). Transformed scores for items contributing to a domain were then averaged into a domain score. Each domain score ranges from 0 (worst experience) to 10 (best experience), higher score=better acceptability. Domain scores common to the Pre & Post SIAQ were analyzed on participants belonging to Pre & Post-SIAQ population and are reported.
Time frame: Baseline (Pre-SIAQ), Week 4, Week 8, Week 12, Week 24, Week 48, Week 72, Week 96
Population: Pre and Post-SIAQ population: participants from the safety population who self-injected the training injection \& completed a Pre-SIAQ before first self-injection, who self-injected study drug at least once during the study and completed a Post-SIAQ. Here, number analyzed = participants with available data at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Feelings about injections: Baseline | 8.6 units on a scale | Standard Deviation 1.8 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Feeling about injections: Week 4 | 9.1 units on a scale | Standard Deviation 1.4 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Feeling about injections: Week 8 | 9.1 units on a scale | Standard Deviation 1.4 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Feeling about injections: Week 12 | 9.2 units on a scale | Standard Deviation 1.4 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Feeling about injections: Week 24 | 9.2 units on a scale | Standard Deviation 1.4 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Feeling about injections: Week 48 | 9.2 units on a scale | Standard Deviation 1.4 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Feeling about injections: Week 72 | 9.2 units on a scale | Standard Deviation 1.4 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Feeling about injections: Week 96 | 9.3 units on a scale | Standard Deviation 1.3 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Self confidence: Baseline | 6.9 units on a scale | Standard Deviation 2.4 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Self Confidence: Week 4 | 8.0 units on a scale | Standard Deviation 2.1 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Self Confidence: Week 8 | 8.1 units on a scale | Standard Deviation 2 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Self Confidence: Week 12 | 8.1 units on a scale | Standard Deviation 1.9 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Self Confidence: Week 24 | 8.0 units on a scale | Standard Deviation 2.1 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Self Confidence: Week 48 | 8.1 units on a scale | Standard Deviation 2.1 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Self Confidence: Week 72 | 8.3 units on a scale | Standard Deviation 2 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Self Confidence: Week 96 | 8.4 units on a scale | Standard Deviation 2 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Satisfaction with self injection: Baseline | 7.2 units on a scale | Standard Deviation 2.5 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Satisfaction with self-injections: Week 4 | 8.5 units on a scale | Standard Deviation 1.6 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Satisfaction with self-injections: Week 8 | 8.7 units on a scale | Standard Deviation 1.6 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Satisfaction with self-injections: Week 12 | 8.7 units on a scale | Standard Deviation 1.6 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Satisfaction with self-injections: Week 24 | 8.6 units on a scale | Standard Deviation 1.8 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Satisfaction with self-injections: Week 48 | 8.7 units on a scale | Standard Deviation 1.5 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Satisfaction with self-injections: Week 72 | 8.8 units on a scale | Standard Deviation 1.7 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Feeling About Injections, Self Confidence, Satisfaction With Self-Injections | Satisfaction with self-injections: Week 96 | 8.8 units on a scale | Standard Deviation 1.4 |
Secondary
Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use
SIAQ: contained 2 modules: Pre-SIAQ and Post-SIAQ. Post-SIAQ: self-completed after self-injection. Post-SIAQ consisted of 21 items grouped into 6 domains: feelings about injections, self-image, self-confidence, injection-site reactions, ease of use & satisfaction with self-injection. Participants rated each item on 5-point (or 6-point) semantic Likert-type scale, where lower numbers indicated a worse experience. Item scores were transformed to obtain a score ranging from 0 (worst experience) to 10 (best experience) for each item. Transformed scores for items contributing to a domain were then averaged into a domain score. Each domain score ranges from 0 (worst experience) to 10 (best experience), higher score=better acceptability. Domain scores which are not in common with Pre-SIAQ were analyzed on the Post-SIAQ population and are reported here.
Time frame: Week 4, Week 8, Week 12, Week 24, Week 48, Week 72, Week 96
Population: POST-SIAQ population: participants from safety population who self-injected at least once during the study and completed a POST-SIAQ regardless of completion of PRE-SIAQ. Here, number analyzed = participants with available data at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Self Image: Week 4 | 9.4 units on a scale | Standard Deviation 1.4 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Self Image: Week 8 | 9.4 units on a scale | Standard Deviation 1.4 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Self Image: Week 12 | 9.4 units on a scale | Standard Deviation 1.4 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Self Image: Week 24 | 9.3 units on a scale | Standard Deviation 1.5 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Self Image: Week 48 | 9.4 units on a scale | Standard Deviation 1.4 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Self Image: Week 72 | 9.3 units on a scale | Standard Deviation 1.5 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Self Image: Week 96 | 9.4 units on a scale | Standard Deviation 1.4 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Injection-site reactions: Week 4 | 9.6 units on a scale | Standard Deviation 0.7 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Injection-site reactions: Week 8 | 9.6 units on a scale | Standard Deviation 0.8 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Injection-site reactions: Week 12 | 9.6 units on a scale | Standard Deviation 0.7 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Injection-site reactions: Week 24 | 9.5 units on a scale | Standard Deviation 0.9 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Injection-site reactions: Week 48 | 9.5 units on a scale | Standard Deviation 0.8 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Injection-site reactions: Week 72 | 9.5 units on a scale | Standard Deviation 0.8 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Injection-site reactions: Week 96 | 9.5 units on a scale | Standard Deviation 0.8 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Ease of use: Week 4 | 8.7 units on a scale | Standard Deviation 1.5 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Ease of use: Week 8 | 8.7 units on a scale | Standard Deviation 1.6 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Ease of use: Week 12 | 8.8 units on a scale | Standard Deviation 1.6 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Ease of use: Week 24 | 8.8 units on a scale | Standard Deviation 1.6 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Ease of use: Week 48 | 8.9 units on a scale | Standard Deviation 1.4 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Ease of use: Week 72 | 9.0 units on a scale | Standard Deviation 1.5 |
| Alirocumab | Assessment of Participant's Acceptability of Self-Injection Using Self Injection Assessment Questionnaire (SIAQ): Self Image, Injection-Site Reactions, Ease of Use | Ease of use: Week 96 | 9.0 units on a scale | Standard Deviation 1.4 |
Secondary
Percentage of Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12
LDL-Cholesterol was calculated using the Friedewald formula. Percentage of participants who reached calculated LDL-C \<100 mg/dL (2.59 mmol/L) at week 12 were reported.
Time frame: At Week 12
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alirocumab | Percentage of Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 12 | 74.6 percentage of participants |
Secondary
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) and/or >=50% Reduction From Baseline in LDL-C at Week 12
LDL-Cholesterol was calculated using the Friedewald formula. Percentage of participants who reached LDL-C \<70 mg/dL at Week 12 and/or \>=50% reduction from baseline in LDL-C at Week 12 are reported.
Time frame: At Week 12
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alirocumab | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) and/or >=50% Reduction From Baseline in LDL-C at Week 12 | 69.1 percentage of participants |
Secondary
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 12
LDL-Cholesterol was calculated using the Friedewald formula. Percentage of participants who reached calculated LDL-C \<70 mg/dL (1.81 mmol/L) at week 12 were reported.
Time frame: At Week 12
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alirocumab | Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 12 | 50.2 percentage of participants |
Secondary
Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
Calculated LDL-C values were obtained using the Friedewald formula. Calculated LDL-C in mg/dL from Friedewald formula (LDL cholesterol = Total cholesterol - HDL cholesterol - \[Triglyceride/5\]). Baseline value was defined as the last observation before the first dose of the treatment.
Time frame: Baseline, Week 12
Population: Analysis was performed on modified intent-to-treat population (mITT): all enrolled participants who received at least one dose or part of a dose of alirocumab and had an evaluable efficacy endpoint during the efficacy treatment period (defined as time period from the first injection of alirocumab up to the day of last injection +21 days).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alirocumab | Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 | -54.84 percent change | Standard Deviation 20.06 |
Secondary
Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12
Baseline value was defined as the last observation before the first dose of the treatment.
Time frame: Baseline, Week 12
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alirocumab | Percent Change From Baseline in High Density Lipoprotein Cholesterol at Week 12 | 4.37 percent change | Standard Deviation 17.29 |
Secondary
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12
Baseline value was defined as the last observation before the first dose of the treatment.
Time frame: Baseline, Week 12
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alirocumab | Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 | -45.89 percent change | Standard Deviation 35.82 |
Secondary
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 12
Baseline value was defined as the last observation before the first dose of the treatment.
Time frame: Baseline, Week 12
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alirocumab | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 12 | -38.28 percent change | Standard Deviation 15.2 |
Secondary
Percent Change From Baseline in Triglycerides at Week 12
Baseline value was defined as the last observation before the first dose of the treatment.
Time frame: Baseline, Week 12
Population: Analysis was performed on mITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alirocumab | Percent Change From Baseline in Triglycerides at Week 12 | -8.28 percent change | Standard Deviation 33.99 |