Primary Objectives: * To demonstrate the superiority of alirocumab in comparison with placebo in the reduction of calculated low-density lipoprotein cholesterol (LDL-C) in participants with diabetes treated with insulin and with hypercholesterolemia at high cardiovascular risk not adequately controlled on maximally tolerated LDL-C lowering therapy. * To evaluate the safety and tolerability of alirocumab in participants with diabetes treated with insulin. Secondary Objective: To demonstrate that alirocumab was superior in comparison to placebo in its effects on other lipid parameters (i.e., measured LDL-C, non-high-density lipoprotein cholesterol \[non-HDL-C\], apolipoprotein B \[Apo B\], total cholesterol \[TC\], lipoprotein a \[Lp(a)\], high density lipoprotein cholesterol \[HDL-C\], triglyceride \[TG\] levels, triglyceride rich lipoproteins \[TGRL\], apolipoprotein A-1 \[Apo A-1\], apolipoprotein C-III \[Apo C-III\], and LDL particle number and size).
The maximum study duration was approximately 9 months per participant, including a 6 month treatment period, a screening period of up to 3 weeks, and an 8 week safety observation period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
517
Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.
Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.
Statins at stable, maximally tolerated dose with or without other LMT as clinically indicated.
Insulin (injectable or inhaled) alone or with other antihyperglycemic drugs as clinically indicated.
Investigational Site Number 840020
Encino, California, United States
Investigational Site Number 840002
Fresno, California, United States
Investigational Site Number 840029
Oakland, California, United States
Investigational Site Number 840027
Loveland, Colorado, United States
Investigational Site Number 840026
Atlantis, Florida, United States
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis
Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
Time frame: From Baseline to Week 24
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)
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).
Time frame: From Baseline up to 10 weeks after last study drug administration (maximum of 32 weeks)
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Time frame: From Baseline to Week 24
Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis
Measured LDL-C values via beta quantification method. Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 24
Percent Change From Baseline in Measured LDL-C at Week 12 - ITT Analysis
Measured LDL-C values via beta quantification method. Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 24
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 24
Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 24
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 24
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Time frame: Up to Week 24
Percentage of Participants Reaching Calculated LDL-C <50 mg/dL (1.3 mmol/L) at Week 24 - On-Treatment Analysis
Adjusted percentages at Week 24 from last observation carried forward (LOCF) approach (for T1DM participants) and multiple imputation approach model (for T2DM participants) including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection). The maximum likelihood estimate did not exist as response rate was zero in a treatment group of T1DM participants.
Time frame: Up to Week 24
Percentage of Participants Reaching Calculated Non-HDL-C <100 mg/dL at Week 24 - On-Treatment Analysis
Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Time frame: Up to Week 24
Percentage of Participants Reaching Calculated Non-HDL-C <80 mg/dL at Week 24 - On-Treatment Analysis
Adjusted percentages at Week 24 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).
Time frame: Up to Week 24
Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach for handling of missing data followed by robust regression model. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model.
Time frame: From Baseline to Week 24
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 24
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
Adjusted means and standard errors at Week 24 from multiple imputation approach for handling of missing data followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 24
Percent Change From Baseline in LDL-C Particle Number at Week 24 - ITT Analysis
LDL-C particle number was calculated from lipid subfractions by nuclear magnetic resonance (NMR) spectroscopy. Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 24
Percent Change From Baseline in LDL-C Particle Size at Week 24 - ITT Analysis
LDL-C particle size was calculated from lipid subfractions by NMR spectroscopy. Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.
Time frame: From Baseline to Week 24
Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24 - ITT Analysis
Absolute change = HbA1c value at specified weeks minus HbA1c value at baseline.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in HbA1c at Weeks 12 and 24 - On-Treatment Analysis
Absolute change = HbA1c value at specified weeks minus HbA1c value at baseline.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 12 and 24 - ITT Analysis
Absolute change = FPG value at specified weeks minus FPG value at baseline.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in FPG at Weeks 12 and 24 - On-Treatment Analysis
Absolute change = FPG value at specified weeks minus FPG value at baseline.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - ITT Analysis
Absolute change = total daily insulin dose at specified weeks minus baseline value.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - On-Treatment Analysis
Absolute change = total daily insulin dose at specified weeks minus baseline value.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - ITT Analysis
Absolute change = daily insulin dose/kg at specified weeks minus baseline value.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - On-Treatment Analysis
Absolute change = daily insulin dose/kg at specified weeks minus baseline value.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - ITT Analysis
Glucose lowering treatment was calculated for non-insulin treatments as one for each unique treatment received and for insulin treatment as one in total for all participants who have taken one or more treatments. Absolute change = number of glucose-lowering treatments at specified weeks minus baseline value.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - On-Treatment Analysis
Glucose lowering treatment was calculated for non-insulin treatments as one for each unique treatment received and for insulin treatment as one in total for all participants who have taken one or more treatments. Absolute change = number of glucose-lowering treatments at specified weeks minus baseline value.
Time frame: Baseline, Weeks 12 and 24
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Investigational Site Number 840006
Bradenton, Florida, United States
Investigational Site Number 840023
Jacksonville, Florida, United States
Investigational Site Number 840028
Palm Harbor, Florida, United States
Investigational Site Number 840022
Ponte Vedra Beach, Florida, United States
Investigational Site Number 840021
Roswell, Georgia, United States
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