Efficacy and Safety of Alirocumab Versus Placebo on Top of Maximally Tolerated Lipid Lowering Therapy in Patients With Hypercholesterolemia Who Have Type 1 or Type 2 Diabetes and Are Treated With Insulin (ODYSSEY DM - Insulin)
- Conditions
- Hypercholesterolaemia
- Interventions
- Registration Number
- NCT02585778
- Lead Sponsor
- Sanofi
- Brief Summary
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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 517
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Alirocumab 75 mg Q2W/Up to 150 mg Q2W Antihyperglycemic Drug Alirocumab 75 mg subcutaneous (SC) injection every 2 weeks (Q2W) added to stable, maximally tolerated dose of statin therapy with or without other lipid-modifying therapy (LMT), insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8. Placebo Q2W Placebo Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab 75 mg Q2W/Up to 150 mg Q2W Lipid-Modifying Therapy (LMT) Alirocumab 75 mg subcutaneous (SC) injection every 2 weeks (Q2W) added to stable, maximally tolerated dose of statin therapy with or without other lipid-modifying therapy (LMT), insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8. Placebo Q2W Lipid-Modifying Therapy (LMT) Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Placebo Q2W Antihyperglycemic Drug Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab Alirocumab 75 mg subcutaneous (SC) injection every 2 weeks (Q2W) added to stable, maximally tolerated dose of statin therapy with or without other lipid-modifying therapy (LMT), insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis From Baseline to Week 24 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).
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) From Baseline up to 10 weeks after last study drug administration (maximum of 32 weeks) 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).
- Secondary Outcome Measures
Name Time Method Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis Up to Week 24 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).
Percentage of Participants Reaching Calculated Non-HDL-C <100 mg/dL at Week 24 - On-Treatment Analysis Up to Week 24 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).
Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - On-Treatment Analysis Baseline, Weeks 12 and 24 Absolute change = daily insulin dose/kg at specified weeks minus baseline value.
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Measured LDL-C at Week 12 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis From Baseline to Week 24 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).
Percentage of Participants Reaching Calculated Non-HDL-C <80 mg/dL at Week 24 - On-Treatment Analysis Up to Week 24 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).
Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24 - ITT Analysis From Baseline to Week 24 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.
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis From Baseline to Week 24 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.
Percentage of Participants Reaching Calculated LDL-C <50 mg/dL (1.3 mmol/L) at Week 24 - On-Treatment Analysis Up to Week 24 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.
Percent Change From Baseline in LDL-C Particle Number at Week 24 - ITT Analysis From Baseline to Week 24 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.
Absolute Change From Baseline in HbA1c at Weeks 12 and 24 - On-Treatment Analysis Baseline, Weeks 12 and 24 Absolute change = HbA1c value at specified weeks minus HbA1c value at baseline.
Percent Change From Baseline in LDL-C Particle Size at Week 24 - ITT Analysis From Baseline to Week 24 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.
Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24 - ITT Analysis Baseline, Weeks 12 and 24 Absolute change = HbA1c value at specified weeks minus HbA1c value at baseline.
Absolute Change From Baseline in FPG at Weeks 12 and 24 - On-Treatment Analysis Baseline, Weeks 12 and 24 Absolute change = FPG value at specified weeks minus FPG value at baseline.
Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - ITT Analysis Baseline, Weeks 12 and 24 Absolute change = total daily insulin dose at specified weeks minus baseline value.
Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - On-Treatment Analysis Baseline, Weeks 12 and 24 Absolute change = total daily insulin dose at specified weeks minus baseline value.
Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - ITT Analysis Baseline, Weeks 12 and 24 Absolute change = daily insulin dose/kg at specified weeks minus baseline value.
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 12 and 24 - ITT Analysis Baseline, Weeks 12 and 24 Absolute change = FPG value at specified weeks minus FPG value at baseline.
Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - ITT Analysis Baseline, Weeks 12 and 24 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.
Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - On-Treatment Analysis Baseline, Weeks 12 and 24 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.
Trial Locations
- Locations (110)
Investigational Site Number 840020
🇺🇸Encino, California, United States
Investigational Site Number 840027
🇺🇸Loveland, Colorado, United States
Investigational Site Number 840029
🇺🇸Oakland, California, United States
Investigational Site Number 840026
🇺🇸Atlantis, 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
Investigational Site Number 840007
🇺🇸Springfield, Illinois, United States
Investigational Site Number 840015
🇺🇸Valparaiso, Indiana, United States
Investigational Site Number 840005
🇺🇸Louisville, Kentucky, United States
Investigational Site Number 840010
🇺🇸Des Moines, Iowa, United States
Investigational Site Number 840018
🇺🇸Auburn, Maine, United States
Investigational Site Number 840013
🇺🇸Hyattsville, Maryland, United States
Investigational Site Number 840016
🇺🇸Rockville, Maryland, United States
Investigational Site Number 840012
🇺🇸Jamaica, New York, United States
Investigational Site Number 840009
🇺🇸Greer, South Carolina, United States
Investigational Site Number 840001
🇺🇸Austin, Texas, United States
Investigational Site Number 040002
🇦🇹Innsbruck, Austria
Investigational Site Number 040005
🇦🇹Linz, Austria
Investigational Site Number 040003
🇦🇹Salzburg, Austria
Investigational Site Number 040001
🇦🇹Wien, Austria
Investigational Site Number 040004
🇦🇹Salzburg, Austria
Investigational Site Number 056002
🇧🇪Edegem, Belgium
Investigational Site Number 056003
🇧🇪Haine-Saint-Paul, Belgium
Investigational Site Number 056001
🇧🇪Leuven, Belgium
Investigational Site Number 250-008
🇫🇷Besancon, France
Investigational Site Number 250-003
🇫🇷Le Creusot, France
Investigational Site Number 250-005
🇫🇷Corbeil Essonnes, France
Investigational Site Number 250-004
🇫🇷La Rochelle Cedex 1, France
Investigational Site Number 250-009
🇫🇷Mulhouse, France
Investigational Site Number 250-002
🇫🇷Nantes cedex 01, France
Investigational Site Number 250-007
🇫🇷Paris, France
Investigational Site Number 250-006
🇫🇷Strasbourg Cedex 2, France
Investigational Site Number 276019
🇩🇪Dresden, Germany
Investigational Site Number 250-001
🇫🇷TOULOUSE Cedex 9, France
Investigational Site Number 276011
🇩🇪Dortmund, Germany
Investigational Site Number 276015
🇩🇪Aschaffenburg, Germany
Investigational Site Number 276002
🇩🇪Berlin, Germany
Investigational Site Number 276009
🇩🇪Dresden, Germany
Investigational Site Number 276014
🇩🇪Dresden, Germany
Investigational Site Number 276021
🇩🇪Hamburg, Germany
Investigational Site Number 276018
🇩🇪Hamburg, Germany
Investigational Site Number 276005
🇩🇪Heidelberg, Germany
Investigational Site Number 276022
🇩🇪Magdeburg, Germany
Investigational Site Number 276013
🇩🇪Lüneburg, Germany
Investigational Site Number 276003
🇩🇪Pirna, Germany
Investigational Site Number 276008
🇩🇪Neumünster, Germany
Investigational Site Number 276017
🇩🇪Neuwied, Germany
Investigational Site Number 276004
🇩🇪Oldenburg, Germany
Investigational Site Number 276010
🇩🇪Saarlouis, Germany
Investigational Site Number 276006
🇩🇪Riesa, Germany
Investigational Site Number 276016
🇩🇪Sulzbach-Rosenberg, Germany
Investigational Site Number 380004
🇮🇹Catania, Italy
Investigational Site Number 380011
🇮🇹Como, Italy
Investigational Site Number 380003
🇮🇹Catanzaro, Italy
Investigational Site Number 380006
🇮🇹Milano, Italy
Investigational Site Number 380007
🇮🇹Milano, Italy
Investigational Site Number 380010
🇮🇹Roma, Italy
Investigational Site Number 528005
🇳🇱Groningen, Netherlands
Investigational Site Number 380012
🇮🇹Verona, Italy
Investigational Site Number 528002
🇳🇱Apeldoorn, Netherlands
Investigational Site Number 528003
🇳🇱Hoogeveen, Netherlands
Investigational Site Number 528001
🇳🇱Rotterdam, Netherlands
Investigational Site Number 528004
🇳🇱Utrecht, Netherlands
Investigational Site Number 724001
🇪🇸Barcelona, Spain
Investigational Site Number 724006
🇪🇸Ferrol, Spain
Investigational Site Number 724007
🇪🇸Badalona, Spain
Investigational Site Number 724005
🇪🇸Madrid, Spain
Investigational Site Number 724004
🇪🇸Madrid, Spain
Investigational Site Number 724013
🇪🇸Granada, Spain
Investigational Site Number 724014
🇪🇸Oviedo, Spain
Investigational Site Number 724002
🇪🇸Pamplona, Spain
Investigational Site Number 724009
🇪🇸Palma de Mallorca, Spain
Investigational Site Number 724011
🇪🇸Majadahonda, Spain
Investigational Site Number 724012
🇪🇸Segovia, Spain
Investigational Site Number 724010
🇪🇸Sant Joan Despí, Spain
Investigational Site Number 724008
🇪🇸Málaga, Spain
Investigational Site Number 724003
🇪🇸Sevilla, Spain
Investigational Site Number 756001
🇨🇭Olten, Switzerland
Investigational Site Number 756003
🇨🇭St. Gallen, Switzerland
Investigational Site Number 826010
🇬🇧Airdrie, United Kingdom
Investigational Site Number 826009
🇬🇧Bournemouth, United Kingdom
Investigational Site Number 826005
🇬🇧Bradford, United Kingdom
Investigational Site Number 826011
🇬🇧Bath, United Kingdom
Investigational Site Number 826004
🇬🇧Bristol, United Kingdom
Investigational Site Number 826001
🇬🇧Burton On Trent, United Kingdom
Investigational Site Number 826015
🇬🇧Durham, United Kingdom
Investigational Site Number 826003
🇬🇧Southampton, United Kingdom
Investigational Site Number 826008
🇬🇧Truro, United Kingdom
Investigational Site Number 826007
🇬🇧Manchester, United Kingdom
Investigational Site Number 826006
🇬🇧Peterborough, United Kingdom
Investigational Site Number 826012
🇬🇧High Wycombe, United Kingdom
Investigational Site Number 826002
🇬🇧Welwyn Garden City, United Kingdom
Investigational Site Number 840006
🇺🇸Bradenton, Florida, United States
Investigational Site Number 840003
🇺🇸Dallas, Texas, United States
Investigational Site Number 840024
🇺🇸Chattanooga, Tennessee, United States
Investigational Site Number 840002
🇺🇸Fresno, California, United States
Investigational Site Number 840017
🇺🇸Ogden, Utah, United States
Investigational Site Number 840014
🇺🇸Maumee, Ohio, United States
Investigational Site Number 840019
🇺🇸Dallas, Texas, United States
Investigational Site Number 840025
🇺🇸Houston, Texas, United States
Investigational Site Number 840011
🇺🇸Indianapolis, Indiana, United States
Investigational Site Number 840004
🇺🇸Minneapolis, Minnesota, United States
Investigational Site Number 840008
🇺🇸Salt Lake City, Utah, United States
Investigational Site Number 380005
🇮🇹Moncalieri, Italy
Investigational Site Number 380009
🇮🇹Napoli, Italy
Investigational Site Number 380008
🇮🇹Padova, Italy
Investigational Site Number 380002
🇮🇹Palermo, Italy
Investigational Site Number 380001
🇮🇹Pisa, Italy