ODYSSEY KIDS: An 8-Week Dose-Finding Study to Evaluate the Efficacy and Safety of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia
Study Details
Study Description
Brief Summary
Primary Objective:
To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 8 weeks of treatment in heterozygous familial hypercholesterolemia (heFH) participants aged of 8 to 17 years, with LDL-C >=130 milligrams per deciliter (mg/dL) (3.37 millimoles per litre [mmol/L]) on optimal stable daily dose of statin therapy +/- other lipid modifying therapies (LMTs) or a stable dose of non-statin LMTs in case of intolerance to statins for at least 4 weeks prior to the screening period.
Secondary Objective:
-
To evaluate the safety and tolerability of alirocumab.
-
To evaluate the pharmacokinetics profile of alirocumab.
-
To evaluate the effects of alirocumab on other lipid parameters.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
For Cohorts 1 to 3, a study duration of approximately 16-23 weeks (screening period: up to 6 (+1) weeks, open-label dose finding treatment period: 8 weeks, follow up period: 6-8 weeks).
For Cohort 4, a study duration of approximately 14-19 weeks (screening period up to 6 [+1] weeks, open-label dose finding treatment period: 12 weeks).
Optional extension period: up to a maximum of 2 years for the first participants enrolled in Cohorts 1 to 3, but a maximum of approximately 5 months for the first participants enrolled in Cohort 4.
For all participants who declined participation in the phase 3 study, their last alirocumab injection was on December 2018.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Cohort 1 - Alirocumab 30 mg Q2W: <50 kg Period 1: Participants with body weight less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram(mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT). Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until they started receiving dose matching to Cohort 2 dosage including dose adjustment to body weight as required. Cohort 2 dosage was: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. |
Drug: alirocumab SAR236553 (REGN727)
Pharmaceutical form: solution Route of administration: subcutaneous injection
Other Names:
Drug: statins
Pharmaceutical form: tablet Route of administration: oral
Drug: ezetimibe
Pharmaceutical form:tablet Route of administration: oral
Drug: cholestyramine
Pharmaceutical form:tablet Route of administration: oral
Drug: fenofibrate
Pharmaceutical form: tablet Route of administration: oral
Drug: omega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral
Drug: nicotinic acid
Pharmaceutical form: tablet Route of administration: oral
|
Experimental: Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg Period 1: Participants with body weight greater than or equal to (>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. |
Drug: alirocumab SAR236553 (REGN727)
Pharmaceutical form: solution Route of administration: subcutaneous injection
Other Names:
Drug: statins
Pharmaceutical form: tablet Route of administration: oral
Drug: ezetimibe
Pharmaceutical form:tablet Route of administration: oral
Drug: cholestyramine
Pharmaceutical form:tablet Route of administration: oral
Drug: fenofibrate
Pharmaceutical form: tablet Route of administration: oral
Drug: omega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral
Drug: nicotinic acid
Pharmaceutical form: tablet Route of administration: oral
|
Experimental: Cohort 2 - Alirocumab 40 mg Q2W: <50 kg Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still < 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. |
Drug: alirocumab SAR236553 (REGN727)
Pharmaceutical form: solution Route of administration: subcutaneous injection
Other Names:
Drug: statins
Pharmaceutical form: tablet Route of administration: oral
Drug: ezetimibe
Pharmaceutical form:tablet Route of administration: oral
Drug: cholestyramine
Pharmaceutical form:tablet Route of administration: oral
Drug: fenofibrate
Pharmaceutical form: tablet Route of administration: oral
Drug: omega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral
Drug: nicotinic acid
Pharmaceutical form: tablet Route of administration: oral
|
Experimental: Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130. |
Drug: alirocumab SAR236553 (REGN727)
Pharmaceutical form: solution Route of administration: subcutaneous injection
Other Names:
Drug: statins
Pharmaceutical form: tablet Route of administration: oral
Drug: ezetimibe
Pharmaceutical form:tablet Route of administration: oral
Drug: cholestyramine
Pharmaceutical form:tablet Route of administration: oral
Drug: fenofibrate
Pharmaceutical form: tablet Route of administration: oral
Drug: omega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral
Drug: nicotinic acid
Pharmaceutical form: tablet Route of administration: oral
|
Experimental: Cohort 3 - Alirocumab 75 mg Q4W: <50 kg Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT. Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. |
Drug: alirocumab SAR236553 (REGN727)
Pharmaceutical form: solution Route of administration: subcutaneous injection
Other Names:
Drug: statins
Pharmaceutical form: tablet Route of administration: oral
Drug: ezetimibe
Pharmaceutical form:tablet Route of administration: oral
Drug: cholestyramine
Pharmaceutical form:tablet Route of administration: oral
Drug: fenofibrate
Pharmaceutical form: tablet Route of administration: oral
Drug: omega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral
Drug: nicotinic acid
Pharmaceutical form: tablet Route of administration: oral
|
Experimental: Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. |
Drug: alirocumab SAR236553 (REGN727)
Pharmaceutical form: solution Route of administration: subcutaneous injection
Other Names:
Drug: statins
Pharmaceutical form: tablet Route of administration: oral
Drug: ezetimibe
Pharmaceutical form:tablet Route of administration: oral
Drug: cholestyramine
Pharmaceutical form:tablet Route of administration: oral
Drug: fenofibrate
Pharmaceutical form: tablet Route of administration: oral
Drug: omega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral
Drug: nicotinic acid
Pharmaceutical form: tablet Route of administration: oral
|
Experimental: Cohort 4 - Alirocumab 150 mg Q4W: <50 kg Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight < 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48. |
Drug: alirocumab SAR236553 (REGN727)
Pharmaceutical form: solution Route of administration: subcutaneous injection
Other Names:
Drug: statins
Pharmaceutical form: tablet Route of administration: oral
Drug: ezetimibe
Pharmaceutical form:tablet Route of administration: oral
Drug: cholestyramine
Pharmaceutical form:tablet Route of administration: oral
Drug: fenofibrate
Pharmaceutical form: tablet Route of administration: oral
Drug: omega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral
Drug: nicotinic acid
Pharmaceutical form: tablet Route of administration: oral
|
Experimental: Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48. |
Drug: alirocumab SAR236553 (REGN727)
Pharmaceutical form: solution Route of administration: subcutaneous injection
Other Names:
Drug: statins
Pharmaceutical form: tablet Route of administration: oral
Drug: ezetimibe
Pharmaceutical form:tablet Route of administration: oral
Drug: cholestyramine
Pharmaceutical form:tablet Route of administration: oral
Drug: fenofibrate
Pharmaceutical form: tablet Route of administration: oral
Drug: omega-3 fatty acids
Pharmaceutical form: tablet Route of administration: oral
Drug: nicotinic acid
Pharmaceutical form: tablet Route of administration: oral
|
Outcome Measures
Primary Outcome Measures
- Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 [Baseline, Week 8]
Percent change in calculated LDL-C was defined as 100*(calculated LDL-C value at Week 8 - calculated LDL-C value at baseline)/calculated LDL-C value at baseline. All available baseline and post-baseline calculated LDL-C value during the OLDFI efficacy treatment period & within one of the analysis windows up to Week 8 were used in the model. OLDFI efficacy treatment period was defined as the period from first investigational medicinal product (IMP) injection to last OLDFI IMP injection + 21 days(for Cohorts 1 & 2) or +35 days (for Cohorts 3 & 4). Adjusted Least-squares (LS) mean & standard error (SE) at Week 8 were obtained from mixed-effect model with repeated measures (MMRM) analysis, with fixed categorical effects of alirocumab dose/dose regimen (30 mg Q2W [<50 kg], 40 mg Q2W [<50 kg], 50 mg Q2W [>=50 kg], 75 mg Q2W [>=50 kg], 75 mg Q4W [<50 kg],150 mg Q4W [>=50 kg], 150 mg Q4W [<50 kg] and 300 mg Q4W ([>=50 kg] dose), time point & dose/dose regimen-by-time point interaction.
Secondary Outcome Measures
- Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 [Baseline, Week 8]
Absolute change in LDL-C was calculated by subtracting baseline value from Week 8 value. Adjusted LS means and SE were obtained using MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction.
- Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8 [At Week 8]
Combined estimate for percentage of participants was obtained by averaging out all the imputed percentage of participants reaching the level of interest. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively; with number of imputations = 1000. In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
- Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8 [At Week 8]
Combined estimate for percentage of participants was obtained by averaging out all the imputed percentage of participants reaching the level of interest. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively; with number of imputations = 1000. In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
- Percent Change From Baseline in Calculated LDL-C at Week 12: Cohort 4 [Baseline, Week 12]
Adjusted LS means and standard error at Week 12 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction.
- Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8 [Baseline, Week 8]
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline value and post-baseline values in at least one of the analysis windows used in the model.
- Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8 [Baseline, Week 8]
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baselines value and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
- Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8 [Baseline, Week 8]
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
- Percent Change From Baseline in Lipoprotein(a) at Week 8 [Baseline, Week 8]
Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively (with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
- Percent Change From Baseline in Fasting Triglyceride at Week 8 [Baseline, Week 8]
Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
- Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8 [Baseline, Week 8]
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
- Percent Change From Baseline in Apolipoprotein A-1 at Week 8 [Baseline, Week 8]
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
- Absolute Change From Baseline in Apolipoprotein B at Week 8 [Baseline, Week 8]
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
- Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8 [Baseline, Week 8]
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
- Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8 [Baseline, Week 8]
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
- Absolute Change From Baseline in Lipoprotein(a) at Week 8 [Baseline, Week 8]
Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
- Absolute Change From Baseline in HDL-C at Week 8 [Baseline, Week 8]
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
- Absolute Change From Baseline in Fasting Triglyceride at Week 8 [Baseline, Week 8]
Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables.
- Absolute Change From Baseline in Apolipoprotein A-1 at Week 8 [Baseline, Week 8]
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
- Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8 [Baseline, Week 8]
Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model.
Eligibility Criteria
Criteria
Inclusion criteria :
-
Children and adolescent male and female participants aged of 8 to 17 years at the time of signed informed consent. For Russia only: Male and female participants aged >=12 and <=17 years at the time of signed informed consent.
-
Participants with diagnosis of heterozygous familial hypercholesterolemia (heFH) through genotyping or clinical criteria.
-
Participants treated with optimal dose of statin +/- other LMT(s) or non-statin LMT(s) if statin intolerant at stable dose for at least 4 weeks prior to screening lipid sampling.
-
Participants with calculated LDL-C greater than or equal to 130 mg/dL (>=3.37 mmol/L) at the screening visit.
-
Participants with body weight greater than or equal to 25 kg.
-
Participants aged of 8 to 9 years to be at Tanner stage 1 and participants aged of 10 to 17 years to be at least at Tanner stage 2 in their development.
-
A signed informed consent indicating parental permission with or without participant assent.
Exclusion criteria:
-
Participant with secondary hyperlipidemia.
-
Diagnosis of homozygous familial hypercholesterolemia.
-
Participant who had received lipid apheresis treatment within 2 months prior to the screening period, or has plans to receive it during the study.
-
Known history of type 1 or type 2 diabetes mellitus.
-
Known history of thyroid disease.
-
Known history of hypertension.
-
Fasting triglycerides >350 mg/dL (3.95 mmol/L).
-
Severe renal impairment (i.e., estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m^2).
-
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 x upper limit of normal (ULN).
-
Creatinine phosphokinase (CPK) >3 x ULN.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Investigational Site Number 8400002 | Saint Louis | Missouri | United States | 63110 |
2 | Investigational Site Number 8400005 | Charlotte | North Carolina | United States | 28204 |
3 | Investigational Site Number 8400001 | Cincinnati | Ohio | United States | 45229 |
4 | Investigational Site Number 1240001 | Quebec | Canada | G1V 4W2 | |
5 | Investigational Site Number 2030001 | Brno | Czechia | 62500 | |
6 | Investigational Site Number 2030003 | Praha 5 - Motol | Czechia | 15006 | |
7 | Investigational Site Number 2030002 | Zlin | Czechia | 76275 | |
8 | Investigational Site Number 2500001 | Bron Cedex | France | 69677 | |
9 | Investigational Site Number 5280001 | Amsterdam | Netherlands | 1105AZ | |
10 | Investigational Site Number 5780001 | Oslo | Norway | ||
11 | Investigational Site Number 6430001 | Kemerovo | Russian Federation | 650002 | |
12 | Investigational Site Number 6430004 | Saint-Petersburg | Russian Federation | 194100 | |
13 | Investigational Site Number 7100001 | Parow | South Africa | 7500 | |
14 | Investigational Site Number 7240004 | A Coruna | Spain | 15001 | |
15 | Investigational Site Number 7240001 | Madrid | Spain | 28009 | |
16 | Investigational Site Number 7520001 | Stockholm | Sweden | 171 76 |
Sponsors and Collaborators
- Sanofi
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Sciences & Operations, Sanofi
Study Documents (Full-Text)
More Information
Publications
None provided.- DFI14223
- 2015-003766-85
- U1111-1178-4764
Study Results
Participant Flow
Recruitment Details | The study was conducted at 16 sites in 10 countries. Overall 63 participants were screened between 15 September 2016 and 13 June 2018, of whom 21 participants were screen failures. Screen failures were mainly due to exclusion criteria met. |
---|---|
Pre-assignment Detail | A total of 42 participants were included in this study. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Period 1: Participants with body weight less than (<) 50 kilograms (kg) received subcutaneous (SC) injection of alirocumab 30 milligram (mg) administered every 2 weeks (Q2W) up to 8 weeks added to lipid modifying therapy (LMT). Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. | Period 1: Participants with body weight greater than or equal to (>=) 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. | Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still < 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. | Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130. | Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. | Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. | Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight < 50 kg received SC injection of Alirocumab 150 mg administered Q4W from Week 12 until Week 48. | Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48. |
Period Title: 12 Weeks Open-Label Dose Finding Period | ||||||||
STARTED | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
Treated | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
COMPLETED | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: 12 Weeks Open-Label Dose Finding Period | ||||||||
STARTED | 3 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
Treated | 3 | 6 | 4 | 6 | 6 | 5 | 5 | 4 |
COMPLETED | 3 | 3 | 4 | 6 | 6 | 5 | 5 | 4 |
NOT COMPLETED | 0 | 3 | 0 | 0 | 0 | 0 | 1 | 1 |
Baseline Characteristics
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Total |
---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W from Week 16 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. | Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W from Week 16 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. | Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W from Week 16 until switch of dosage in Cohorts 1 and 3. If body weight was still < 50 kg, participants continued to receive SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. | Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W from Week 16 until Week 130. | Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered every 4 weeks (Q4W) up to 8 weeks added to LMT. Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W from Week 14 until switch to Cohort 2 dosage including dose adjustment to body weight as required, then Cohort 2 dosage: if body weight was still < 50 kg, participants received SC injection of alirocumab 40 mg administered Q2W until Week 130; if body weight was > = 50 kg participants received SC injection of alirocumab 75 mg administered Q2W until Week 130. | Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 14 until switch to Cohort 2 dosage then SC injection of alirocumab 75 mg administered Q2W until Week 130. | Period 1: Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W from Week 12 until Week 48. | Period 1: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. Period 2: Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W from Week 12 until Week 48. | Total of all reporting groups |
Overall Participants | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 | 42 |
Age (years) [Mean (Standard Deviation) ] | |||||||||
Mean (Standard Deviation) [years] |
11.0
(2.0)
|
13.8
(2.7)
|
11.3
(2.2)
|
14.3
(2.3)
|
9.8
(1.9)
|
13.8
(1.6)
|
11.3
(2.2)
|
13.6
(2.1)
|
12.4
(2.6)
|
Sex: Female, Male (Count of Participants) | |||||||||
Female |
2
50%
|
4
66.7%
|
2
50%
|
2
33.3%
|
3
50%
|
3
60%
|
1
16.7%
|
2
40%
|
19
45.2%
|
Male |
2
50%
|
2
33.3%
|
2
50%
|
4
66.7%
|
3
50%
|
2
40%
|
5
83.3%
|
3
60%
|
23
54.8%
|
Race/Ethnicity, Customized (Count of Participants) | |||||||||
Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
40%
|
2
4.8%
|
Black or African American/White |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
1
2.4%
|
White |
4
100%
|
6
100%
|
4
100%
|
6
100%
|
5
83.3%
|
5
100%
|
6
100%
|
3
60%
|
39
92.9%
|
Low Density Lipoprotein Cholesterol (LDL-C) (millimoles per litre (mmol/L)) [Mean (Standard Deviation) ] | |||||||||
Mean (Standard Deviation) [millimoles per litre (mmol/L)] |
5.169
(0.736)
|
4.339
(1.200)
|
3.596
(0.630)
|
4.510
(1.052)
|
4.337
(1.147)
|
4.642
(1.272)
|
5.100
(1.136)
|
4.641
(0.926)
|
4.6
(1.1)
|
Outcome Measures
Title | Percent Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 |
---|---|
Description | Percent change in calculated LDL-C was defined as 100*(calculated LDL-C value at Week 8 - calculated LDL-C value at baseline)/calculated LDL-C value at baseline. All available baseline and post-baseline calculated LDL-C value during the OLDFI efficacy treatment period & within one of the analysis windows up to Week 8 were used in the model. OLDFI efficacy treatment period was defined as the period from first investigational medicinal product (IMP) injection to last OLDFI IMP injection + 21 days(for Cohorts 1 & 2) or +35 days (for Cohorts 3 & 4). Adjusted Least-squares (LS) mean & standard error (SE) at Week 8 were obtained from mixed-effect model with repeated measures (MMRM) analysis, with fixed categorical effects of alirocumab dose/dose regimen (30 mg Q2W [<50 kg], 40 mg Q2W [<50 kg], 50 mg Q2W [>=50 kg], 75 mg Q2W [>=50 kg], 75 mg Q4W [<50 kg],150 mg Q4W [>=50 kg], 150 mg Q4W [<50 kg] and 300 mg Q4W ([>=50 kg] dose), time point & dose/dose regimen-by-time point interaction. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on modified intent-to-treat (mITT) population which included all participants who received at least one dose or partial dose of IMP injection and had an evaluable outcome measure during the open-label dose finding efficacy treatment period. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
Least Squares Mean (Standard Error) [percent change] |
-41.1
(12.6)
|
-7.9
(10.3)
|
-40.6
(13.2)
|
-49.8
(10.6)
|
-17.5
(10.3)
|
4.0
(11.2)
|
-31.9
(10.3)
|
-59.8
(11.2)
|
Title | Absolute Change From Baseline in Calculated Low Density Lipoprotein Cholesterol (LDL-C) at Week 8 |
---|---|
Description | Absolute change in LDL-C was calculated by subtracting baseline value from Week 8 value. Adjusted LS means and SE were obtained using MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 milligram(mg) administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
Least Squares Mean (Standard Error) [milligram per deciliter (mg/dL)] |
-83.7
(19.5)
|
-27.6
(15.9)
|
-55.5
(20.8)
|
-88.3
(16.5)
|
-32.4
(15.9)
|
0.1
(17.4)
|
-55.9
(15.9)
|
-104.3
(17.4)
|
Title | Percentage of Participants Achieving Calculated Low Density Lipoprotein Cholesterol (LDL-C) <130 mg/dL (3.37 mmol/L) at Week 8 |
---|---|
Description | Combined estimate for percentage of participants was obtained by averaging out all the imputed percentage of participants reaching the level of interest. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively; with number of imputations = 1000. In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. |
Time Frame | At Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 milligram(mg) administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
Number [percentage of participants] |
100.0
2500%
|
33.3
555%
|
97.6
2440%
|
83.0
1383.3%
|
33.3
555%
|
20.0
400%
|
66.7
1111.7%
|
80.0
1600%
|
Title | Percentage of Participants Achieving Calculated LDL-C <110 mg/dL (2.84 mmol/L) at Week 8 |
---|---|
Description | Combined estimate for percentage of participants was obtained by averaging out all the imputed percentage of participants reaching the level of interest. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively; with number of imputations = 1000. In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. |
Time Frame | At Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 milligram (mg) administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
Number [percentage of participants] |
0.0
0%
|
0.0
0%
|
93.4
2335%
|
65.7
1095%
|
16.7
278.3%
|
20.0
400%
|
66.7
1111.7%
|
80.0
1600%
|
Title | Percent Change From Baseline in Calculated LDL-C at Week 12: Cohort 4 |
---|---|
Description | Adjusted LS means and standard error at Week 12 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. |
Time Frame | Baseline, Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. Data for this outcome measure was planned to be collected for Cohort 4 only. |
Arm/Group Title | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 6 | 5 |
Least Squares Mean (Standard Error) [percent change] |
-29.7
(6.9)
|
-49.2
(7.5)
|
Title | Percent Change From Baseline in Apolipoprotein (Apo) B at Week 8 |
---|---|
Description | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline value and post-baseline values in at least one of the analysis windows used in the model. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. Here, overall number of participants analyzed=participants with available data for this outcome measure. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 milligram(mg) administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 3 | 6 | 3 | 6 | 6 | 5 | 6 | 5 |
Least Squares Mean (Standard Error) [percent change] |
-38.4
(12.8)
|
-9.7
(9.1)
|
-36.4
(12.8)
|
-40.1
(9.9)
|
-12.6
(9.1)
|
-0.9
(9.9)
|
-27.2
(9.1)
|
-51.4
(9.9)
|
Title | Percent Change From Baseline in Non-High Density Lipoprotein (HDL-C) at Week 8 |
---|---|
Description | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baselines value and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
Least Squares Mean (Standard Error) [percent change] |
-39.6
(11.9)
|
-7.1
(9.7)
|
-39.7
(12.5)
|
-43.9
(10.0)
|
-14.4
(9.7)
|
3.2
(10.7)
|
-31.5
(9.7)
|
-54.6
(10.7)
|
Title | Percent Change From Baseline in Total Cholesterol (Total-C) at Week 8 |
---|---|
Description | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
Least Squares Mean (Standard Error) [percent change] |
-29.0
(9.7)
|
-4.1
(7.9)
|
-28.6
(10.1)
|
-34.2
(8.1)
|
-10.7
(7.9)
|
5.2
(8.6)
|
-24.0
(7.9)
|
-41.8
(8.6)
|
Title | Percent Change From Baseline in Lipoprotein(a) at Week 8 |
---|---|
Description | Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population in the two steps respectively (with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
Mean (Standard Error) [percent change] |
4.5
(21.1)
|
-26.9
(11.6)
|
1.5
(15.1)
|
-25.2
(14.4)
|
2.2
(10.5)
|
-7.7
(11.4)
|
0.1
(10.2)
|
-7.7
(11.1)
|
Title | Percent Change From Baseline in Fasting Triglyceride at Week 8 |
---|---|
Description | Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
Mean (Standard Error) [percent change] |
-0.4
(19.6)
|
-4.0
(16.0)
|
-7.4
(28.4)
|
14.5
(19.0)
|
19.3
(16.0)
|
-3.1
(17.5)
|
-32.1
(16.0)
|
-7.1
(17.5)
|
Title | Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 8 |
---|---|
Description | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
Least Squares Mean (Standard Error) [percent change] |
9.7
(7.1)
|
16.5
(5.8)
|
14.7
(7.7)
|
10.6
(6.1)
|
5.2
(5.8)
|
13.8
(6.4)
|
4.5
(5.8)
|
2.8
(6.4)
|
Title | Percent Change From Baseline in Apolipoprotein A-1 at Week 8 |
---|---|
Description | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 3 | 6 | 3 | 5 | 6 | 5 | 6 | 5 |
Least Squares Mean (Standard Error) [percent change] |
4.4
(7.2)
|
14.8
(5.1)
|
10.7
(7.2)
|
1.8
(5.6)
|
8.9
(5.1)
|
7.4
(5.6)
|
5.8
(5.1)
|
7.2
(5.6)
|
Title | Absolute Change From Baseline in Apolipoprotein B at Week 8 |
---|---|
Description | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 3 | 6 | 3 | 5 | 6 | 5 | 6 | 5 |
Least Squares Mean (Standard Error) [mg/dL] |
-51.7
(15.8)
|
-18.5
(11.1)
|
-35.3
(15.8)
|
-53.4
(12.2)
|
-15.3
(11.1)
|
-5.4
(12.2)
|
-34.2
(11.1)
|
-63.5
(12.2)
|
Title | Absolute Change From Baseline in Non-High-Density Lipoprotein (Non-HDL-C) at Week 8 |
---|---|
Description | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
Least Squares Mean (Standard Error) [mg/dL] |
-86.1
(20.8)
|
-28.7
(17.0)
|
-62.7
(22.1)
|
-88.5
(17.6)
|
-29.5
(17.0)
|
-0.6
(18.6)
|
-63.1
(17.0)
|
-106.4
(18.6)
|
Title | Absolute Change From Baseline in Total Cholesterol (Total-C) at Week 8 |
---|---|
Description | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
Least Squares Mean (Standard Error) [mg/dL] |
-80.1
(21.4)
|
-20.8
(17.5)
|
-57.1
(22.8)
|
-84.4
(18.1)
|
-27.2
(17.5)
|
5.3
(19.1)
|
-60.7
(17.5)
|
-105.1
(19.1)
|
Title | Absolute Change From Baseline in Lipoprotein(a) at Week 8 |
---|---|
Description | Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
Least Squares Mean (Standard Error) [gram/Liter (g/L)] |
0.003
(0.022)
|
-0.021
(0.017)
|
0.007
(0.073)
|
-0.025
(0.020)
|
0.023
(0.018)
|
-0.031
(0.019)
|
-0.002
(0.017)
|
-0.120
(0.020)
|
Title | Absolute Change From Baseline in HDL-C at Week 8 |
---|---|
Description | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
Least Squares Mean (Standard Error) [mg/dL] |
5.9
(3.4)
|
7.7
(2.8)
|
5.5
(3.7)
|
4.9
(2.9)
|
2.4
(2.8)
|
5.9
(3.1)
|
2.2
(2.8)
|
1.2
(3.1)
|
Title | Absolute Change From Baseline in Fasting Triglyceride at Week 8 |
---|---|
Description | Combined estimates and SE were obtained by combining adjusted means and SE from robust regression model analyses of the different imputed data sets. The robust regression models included the fixed categorical effect of alirocumab dose/dose regimen. A two-step multiple imputation procedure was used to address missing values in the mITT population (in the two steps respectively; with number of imputations = 1000). In the first step, the monotone missing pattern was induced in the multiply-imputed data. In the second step, the missing data at subsequent visits were imputed using the regression method for continuous variables. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 4 | 6 | 4 | 6 | 6 | 5 | 6 | 5 |
Least Squares Mean (Standard Error) [mmol/L] |
-0.121
(0.193)
|
-0.076
(0.157)
|
0.168
(0.226)
|
0.111
(0.188)
|
0.117
(0.157)
|
-0.045
(0.172)
|
-0.402
(0.157)
|
-0.107
(0.172)
|
Title | Absolute Change From Baseline in Apolipoprotein A-1 at Week 8 |
---|---|
Description | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 3 | 6 | 3 | 5 | 6 | 5 | 6 | 5 |
Least Squares Mean (Standard Error) [mg/dL] |
4.0
(9.3)
|
17.7
(6.5)
|
11.3
(9.3)
|
-0.4
(7.2)
|
10.5
(6.5)
|
8.0
(7.2)
|
7.5
(6.5)
|
11.0
(7.2)
|
Title | Absolute Change From Baseline in Ratio Apolipoprotein B/Apolipoprotein A-1 at Week 8 |
---|---|
Description | Adjusted LS means and SE at Week 8 were obtained from MMRM analysis, with fixed categorical effects of alirocumab dose/dose regimen, time point and dose/dose regimen-by-time point interaction. All available baseline values and post-baseline values in at least one of the analysis windows up to Week 8 were used in the model. |
Time Frame | Baseline, Week 8 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure. |
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to 8 weeks added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to Week 8 added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to 12 weeks added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to 12 weeks added to LMT. |
Measure Participants | 3 | 6 | 3 | 5 | 6 | 5 | 6 | 5 |
Least Squares Mean (Standard Error) [ratio (Apo B/Apo A-1)] |
-0.363
(0.123)
|
-0.262
(0.087)
|
-0.370
(0.123)
|
-0.402
(0.096)
|
-0.190
(0.087)
|
-0.086
(0.096)
|
-0.282
(0.087)
|
-0.473
(0.096)
|
Adverse Events
Time Frame | All Adverse Events (AEs) were collected from the time of first dose of IMP up to the end of study (Week 152) regardless of seriousness or relationship to investigational product. | |||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days). Participants from Cohorts 1, 2 and 3 had an option to switch to cohort 2 dosage according to their weight category. 7 participants from Cohort 1 and 11 participants from Cohort 2 and 3 switched the dosage. Analysis was performed on safety population. | |||||||||||||||||||
Arm/Group Title | Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Alirocumab 40 Q2W Post-switch | Alirocumab 75 Q2W Post-switch | ||||||||||
Arm/Group Description | Participants with body weight < 50 kg received SC injection of alirocumab 30 mg administered Q2W up to the switch of dosage added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 50 mg administered Q2W up to the switch of dosage added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 40 mg administered Q2W up to the switch of dosage added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 75 mg administered Q2W up to the switch of dosage added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 75 mg administered Q4W up to the switch of dosage added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 150 mg administered Q4W up to the switch of dosage added to LMT. | Participants with body weight < 50 kg received SC injection of alirocumab 150 mg administered Q4W up to the end of the OLE period (up to 130 weeks) added to LMT. | Participants with body weight >= 50 kg received SC injection of alirocumab 300 mg administered Q4W up to the end of the OLE period (up to 130 weeks) added to LMT. | Participants with body weight < 50 kg from cohort 1, 2 and 3 switched to dosage and received SC injection of alirocumab 40 mg administered Q2W from the switch up to the end of the OLE period (up to 130 weeks) added to LMT. | Participants from Cohort 1 (7 participants), Cohort 2 and Cohort 3 (11 participants) switched to dosage and received SC injection of alirocumab 75 mg administered Q2W up to the end of the OLE period (up to 130 weeks) added to LMT. | ||||||||||
All Cause Mortality |
||||||||||||||||||||
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Alirocumab 40 Q2W Post-switch | Alirocumab 75 Q2W Post-switch | |||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/4 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/10 (0%) | 0/18 (0%) | ||||||||||
Serious Adverse Events |
||||||||||||||||||||
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Alirocumab 40 Q2W Post-switch | Alirocumab 75 Q2W Post-switch | |||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/4 (0%) | 0/6 (0%) | 0/4 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/10 (0%) | 0/18 (0%) | ||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||
Cohort 1 - Alirocumab 30 mg Q2W: <50 kg | Cohort 1 - Alirocumab 50 mg Q2W: >=50 kg | Cohort 2 - Alirocumab 40 mg Q2W: <50 kg | Cohort 2 - Alirocumab 75 mg Q2W: >=50 kg | Cohort 3 - Alirocumab 75 mg Q4W: <50 kg | Cohort 3 - Alirocumab 150 mg Q4W: >=50 kg | Cohort 4 - Alirocumab 150 mg Q4W: <50 kg | Cohort 4 - Alirocumab 300 mg Q4W: >=50 kg | Alirocumab 40 Q2W Post-switch | Alirocumab 75 Q2W Post-switch | |||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 4/4 (100%) | 5/6 (83.3%) | 1/4 (25%) | 4/6 (66.7%) | 5/6 (83.3%) | 3/5 (60%) | 3/6 (50%) | 4/5 (80%) | 7/10 (70%) | 9/18 (50%) | ||||||||||
Blood and lymphatic system disorders | ||||||||||||||||||||
Lymphadenopathy | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Neutropenia | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Eye disorders | ||||||||||||||||||||
Excessive Eye Blinking | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Gastrointestinal disorders | ||||||||||||||||||||
Abdominal Discomfort | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Abdominal Pain | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
Constipation | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
Diarrhoea | 0/4 (0%) | 0 | 2/6 (33.3%) | 2 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 1/6 (16.7%) | 1 | 1/5 (20%) | 1 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Nausea | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 2 |
Toothache | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Vomiting | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
General disorders | ||||||||||||||||||||
Fatigue | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
Influenza Like Illness | 1/4 (25%) | 1 | 1/6 (16.7%) | 4 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 1/10 (10%) | 2 | 0/18 (0%) | 0 |
Injection Site Reaction | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 2 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Immune system disorders | ||||||||||||||||||||
Food Allergy | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Infections and infestations | ||||||||||||||||||||
Abscess Limb | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
Cystitis Bacterial | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
Cytomegalovirus Hepatitis | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
Ear Infection | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/10 (10%) | 1 | 1/18 (5.6%) | 1 |
Gastroenteritis Viral | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 3/10 (30%) | 3 | 1/18 (5.6%) | 2 |
Infectious Mononucleosis | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Nasopharyngitis | 1/4 (25%) | 1 | 2/6 (33.3%) | 5 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/10 (10%) | 2 | 2/18 (11.1%) | 2 |
Otitis Externa | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/10 (10%) | 2 | 0/18 (0%) | 0 |
Otitis Media | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Pharyngitis | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Pharyngitis Streptococcal | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
Post Procedural Infection | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Pyelonephritis | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Sinusitis | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Tonsillitis | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
Upper Respiratory Tract Infection | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 2 | 1/6 (16.7%) | 1 | 1/5 (20%) | 2 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 1/10 (10%) | 1 | 0/18 (0%) | 0 |
Urinary Tract Infection | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
Varicella | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/10 (10%) | 1 | 0/18 (0%) | 0 |
Viral Upper Respiratory Tract Infection | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
Vulvovaginal Mycotic Infection | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
Injury, poisoning and procedural complications | ||||||||||||||||||||
Animal Scratch | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Arthropod Bite | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Concussion | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Fall | 1/4 (25%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Hand Fracture | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
Ligament Sprain | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 2/18 (11.1%) | 2 |
Post-Traumatic Pain | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Radius Fracture | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Road Traffic Accident | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Traumatic Haematoma | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Investigations | ||||||||||||||||||||
Blood Follicle Stimulating Hormone Decreased | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Blood Luteinising Hormone Decreased | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Low Density Lipoprotein Decreased | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||||||||||||||
Type 1 Diabetes Mellitus | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Vitamin D Deficiency | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 1/10 (10%) | 1 | 0/18 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||||||||||||
Arthritis | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Flank Pain | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Muscle Spasms | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Myalgia | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Tendon Pain | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||
Pyogenic Granuloma | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Nervous system disorders | ||||||||||||||||||||
Headache | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/10 (10%) | 2 | 0/18 (0%) | 0 |
Hypoaesthesia | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Presyncope | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Syncope | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
Thoracic Outlet Syndrome | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
Psychiatric disorders | ||||||||||||||||||||
Alcohol Abuse | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Anxiety Disorder | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
Depressed Mood | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Reproductive system and breast disorders | ||||||||||||||||||||
Premenstrual Pain | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||
Asthma | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Epistaxis | 1/4 (25%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 1/6 (16.7%) | 1 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 1/18 (5.6%) | 1 |
Oropharyngeal Pain | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Sinus Congestion | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||||||||||||||||
Acne | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 1/5 (20%) | 1 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Vascular disorders | ||||||||||||||||||||
Pallor | 0/4 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/6 (0%) | 0 | 0/5 (0%) | 0 | 0/10 (0%) | 0 | 0/18 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Results Point of Contact
Name/Title | Trial Transparency Team |
---|---|
Organization | Sanofi aventis recherche & développement |
Phone | 800-633-1610 ext 1# |
Contact-US@sanofi.com |
- DFI14223
- 2015-003766-85
- U1111-1178-4764