Efficacy and Safety of Alirocumab Versus Usual Care on Top of Maximally Tolerated Statin Therapy in Patients With Type 2 Diabetes and Mixed Dyslipidemia (ODYSSEY DM-Dyslipidemia)
- Conditions
- Dyslipidemia
- Interventions
- Drug: StatinsDrug: Antihyperglycemic Drug
- Registration Number
- NCT02642159
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To demonstrate the superiority of alirocumab in comparison with usual care in the reduction of non-high-density lipoprotein cholesterol (non-HDL-C) in participants with type 2 diabetes and mixed dyslipidemia at high cardiovascular risk with non-HDL-C not adequately controlled with maximally tolerated statin therapy.
Secondary Objectives:
* To demonstrate whether alirocumab is superior in comparison with usual care in its effects on other lipid parameters (ie, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), total cholesterol (Total -C), lipoprotein a (Lp\[a\]), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), triglyceride rich lipoproteins (TGRLs), apolipoprotein A-1 (Apo A-1), apolipoprotein C-III (Apo C-III), lipid subfractions by nuclear magnetic resonance (NMR) spectroscopy (ie, LDL-C particle size and LDL, very low-density lipoprotein \[VLDL\], HDL, and intermediate-density lipoprotein \[IDL\] particle number).
* To assess changes in glycemic parameters with alirocumab vs. usual care treatment.
* To demonstrate the safety and tolerability of alirocumab.
* To evaluate treatment acceptance of alirocumab.
* To evaluate proprotein convertase subtilisin kexin type 9 (PCSK9) concentrations and antibody development.
* To demonstrate the superiority of alirocumab vs. fenofibrate on non-HDL-C and other lipid parameters (subgroup analysis).
- 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.
For the purpose of scientific communication, a first-step analysis (both efficacy and safety) was performed at the Week 24 cut-off date. A second-step analysis was performed once all participants had completed the study to include a final update of the safety analysis.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 413
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 Statins Alirocumab 75 mg subcutaneous (SC) injection every 2 weeks (Q2W) added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other lipid modifying therapy (LMT) for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-high-density lipoprotein cholesterol (non-HDL-C) levels \>=100 mg/dL (2.59 mmol/L) at Week 8. Alirocumab 75 mg Q2W/Up to 150 mg Q2W Antihyperglycemic Drug Alirocumab 75 mg subcutaneous (SC) injection every 2 weeks (Q2W) added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other lipid modifying therapy (LMT) for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-high-density lipoprotein cholesterol (non-HDL-C) levels \>=100 mg/dL (2.59 mmol/L) at Week 8. Usual Care Statins Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks. Usual Care Omega-3 fatty acids Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks. Usual Care Antihyperglycemic Drug Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment 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 insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other lipid modifying therapy (LMT) for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-high-density lipoprotein cholesterol (non-HDL-C) levels \>=100 mg/dL (2.59 mmol/L) at Week 8. Usual Care Nicotinic acid Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks. Usual Care Fenofibrate Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks. Usual Care Ezetimibe Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Non-HDL-C at Week 24: Overall 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 8 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
Percent Change From Baseline in Non-HDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum 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 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Measured Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24: Overall 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 8 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Measured LDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum 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 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Percent Change From Baseline in Non-HDL-C at Week 12: Overall ITT Analysis From Baseline to Week 24 Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Non-HDL-C at Week 12: ITT- Intent to Prescribe Fenofibrate Stratum From Baseline to Week 24 Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Percent Change From Baseline in Measured LDL-C at Week 12: Overall 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 8 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Measured LDL-C at Week 12: ITT- Intent to Prescribe Fenofibrate Stratum 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 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24: Overall 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 8 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Apo B at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum 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 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 : Overall 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 8 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Total-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum 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 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Percent Change From Baseline in Lipoprotein(a) at Week 24 : Overall ITT Analysis From Baseline to Week 24 Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach followed by robust regression model for handling of missing data. All available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment were included in the imputation model.
Percent Change From Baseline in Lipoprotein(a) at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum From Baseline to Week 24 Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Percent Change From Baseline in Fasting Triglycerides at Week 24: Overall ITT Analysis From Baseline to Week 24 Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in Fasting Triglycerides at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum From Baseline to Week 24 Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Percent Change From Baseline in HDL-C at Week 24 : Overall 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 8 to Week 24 regardless of status on- or off-treatment.
Percent Change From Baseline in HDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum 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 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Percent Change From Baseline in LDL-C Particle Number at Week 24: Overall 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 8 to Week 24 regardless of status on- or off-treatment.
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 and 24 : Overall ITT Analysis Baseline, Week 12 and 24 Absolute change = FPG value at specified week minus FPG value at baseline.
Percent Change From Baseline in LDL-C Particle Number at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum From Baseline to Week 24 LDL-C particle number was calculated from lipid subfractions by NMR spectroscopy. Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.
Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Week 12 and 24 : Overall ITT Analysis Baseline, Week 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 week minus baseline value.
Absolute Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 and 24 : Overall ITT Analysis Baseline, Week 12 and 24 Absolute change = HbA1c value at specified week minus HbA1c value at baseline.
Trial Locations
- Locations (119)
Investigational Site Number 840-156
šŗšøTustin, California, United States
Investigational Site Number 246101
š«š®Oulu, Finland
Investigational Site Number 840-118
šŗšøLos Angeles, California, United States
Investigational Site Number 840-161
šŗšøChicago, Illinois, United States
Investigational Site Number 840-101
šŗšøLas Vegas, Nevada, United States
Investigational Site Number 840-140
šŗšøLas Vegas, Nevada, United States
Investigational Site Number 840-143
šŗšøHouston, Texas, United States
Investigational Site Number 840-168
šŗšøHouston, Texas, United States
Investigational Site Number 826104
š¬š§Exeter, United Kingdom
Investigational Site Number 276108
š©šŖEssen, Germany
Investigational Site Number 840-169
šŗšøStockbridge, Georgia, United States
Investigational Site Number 076104
š§š·Fortaleza, Brazil
Investigational Site Number 840-106
šŗšøNorthridge, California, United States
Investigational Site Number 840-137
šŗšøBainbridge, Georgia, United States
Investigational Site Number 840-141
šŗšøFresno, California, United States
Investigational Site Number 840-176
šŗšøPort Hueneme, California, United States
Investigational Site Number 840-184
šŗšøCrystal Lake, Illinois, United States
Investigational Site Number 840-163
šŗšøLittle Rock, Arkansas, United States
Investigational Site Number 840-122
šŗšøTarzana, California, United States
Investigational Site Number 840-107
šŗšøBoca Raton, Florida, United States
Investigational Site Number 840-132
šŗšøOcoee, Florida, United States
Investigational Site Number 840-183
šŗšøPaducah, Kentucky, United States
Investigational Site Number 840-179
šŗšøOviedo, Florida, United States
Investigational Site Number 840-157
šŗšøNew York, New York, United States
Investigational Site Number 840-104
šŗšøColumbus, Ohio, United States
Investigational Site Number 840-105
šŗšøMarion, Ohio, United States
Investigational Site Number 840-187
šŗšøMurrells Inlet, South Carolina, United States
Investigational Site Number 840-175
šŗšøMaumee, Ohio, United States
Investigational Site Number 840-147
šŗšøChattanooga, Tennessee, United States
Investigational Site Number 076105
š§š·SĆ£o paulo, Brazil
Investigational Site Number 380107
š®š¹Catanzaro, Italy
Investigational Site Number 380103
š®š¹Napoli, Italy
Investigational Site Number 380108
š®š¹Padova, Italy
Investigational Site Number 380106
š®š¹Partinico, Italy
Investigational Site Number 380102
š®š¹Torino, Italy
Investigational Site Number 380104
š®š¹Bergamo, Italy
Investigational Site Number 376102
š®š±Rehovot, Israel
Investigational Site Number 792106
š¹š·Ankara, Turkey
Investigational Site Number 792108
š¹š·Corum, Turkey
Investigational Site Number 792103
š¹š·Samsun, Turkey
Investigational Site Number 826103
š¬š§Stevenage, United Kingdom
Investigational Site Number 826102
š¬š§West Bromwich, United Kingdom
Investigational Site Number 840-159
šŗšøKnoxville, Tennessee, United States
Investigational Site Number 840-170
šŗšøBoynton Beach, Florida, United States
Investigational Site Number 840-160
šŗšøVan Nuys, California, United States
Investigational Site Number 840-152
šŗšøHuntington Beach, California, United States
Investigational Site Number 840-115
šŗšøLa Jolla, California, United States
Investigational Site Number 792102
š¹š·Ankara, Turkey
Investigational Site Number 840-114
šŗšøBradenton, Florida, United States
Investigational Site Number 840-167
šŗšøIdaho Falls, Idaho, United States
Investigational Site Number 840-128
šŗšøColumbus, Georgia, United States
Investigational Site Number 840-138
šŗšøSpringfield, Illinois, United States
Investigational Site Number 840-174
šŗšøEvanston, Illinois, United States
Investigational Site Number 076101
š§š·Sao Paulo, Brazil
Investigational Site Number 840-113
šŗšøJefferson City, Missouri, United States
Investigational Site Number 840-120
šŗšøSaint Louis, Missouri, United States
Investigational Site Number 840-190
šŗšøMetairie, Louisiana, United States
Investigational Site Number 840-151
šŗšøRockville, Maryland, United States
Investigational Site Number 840-181
šŗšøNew York, New York, United States
Investigational Site Number 840-188
šŗšøGreensboro, North Carolina, United States
Investigational Site Number 840-131
šŗšøMorehead City, North Carolina, United States
Investigational Site Number 840-158
šŗšøMorganton, North Carolina, United States
Investigational Site Number 840-129
šŗšøFargo, North Dakota, United States
Investigational Site Number 840-136
šŗšøBend, Oregon, United States
Investigational Site Number 840-111
šŗšøSummerville, South Carolina, United States
Investigational Site Number 840-153
šŗšøDallas, Texas, United States
Investigational Site Number 840-142
šŗšøRound Rock, Texas, United States
Investigational Site Number 840-133
šŗšøTomball, Texas, United States
Investigational Site Number 840-150
šŗšøSalt Lake City, Utah, United States
Investigational Site Number 036104
š¦šŗMerewether, Australia
Investigational Site Number 076103
š§š·Campinas, Brazil
Investigational Site Number 036102
š¦šŗHerston, Australia
Investigational Site Number 036101
š¦šŗSt Leonards, Australia
Investigational Site Number 076106
š§š·SĆ£o Paulo, Brazil
Investigational Site Number 076102
š§š·SĆ£O Paulo, Brazil
Investigational Site Number 246102
š«š®Oulu, Finland
Investigational Site Number 246104
š«š®Tampere, Finland
Investigational Site Number 276109
š©šŖBerlin, Germany
Investigational Site Number 276101
š©šŖDresden, Germany
Investigational Site Number 276112
š©šŖBerlin, Germany
Investigational Site Number 276110
š©šŖEssen, Germany
Investigational Site Number 276111
š©šŖGoch, Germany
Investigational Site Number 276107
š©šŖKarlsruhe, Germany
Investigational Site Number 276103
š©šŖKĆ¼nzing, Germany
Investigational Site Number 376104
š®š±Petach tikva, Israel
Investigational Site Number 276102
š©šŖOldenburg in Holstein, Germany
Investigational Site Number 376101
š®š±Beer Sheva, Israel
Investigational Site Number 376103
š®š±Petach Tikva, Israel
Investigational Site Number 414101
š°š¼Kuwait, Kuwait
Investigational Site Number 578102
š³š“Oslo, Norway
Investigational Site Number 380105
š®š¹Roma, Italy
Investigational Site Number 380101
š®š¹Pisa, Italy
Investigational Site Number 422101
š±š§Beirut, Lebanon
Investigational Site Number 578101
š³š“Oslo, Norway
Investigational Site Number 422102
š±š§Hazmieh, Lebanon
Investigational Site Number 752102
šøšŖGƶteborg, Sweden
Investigational Site Number 752101
šøšŖStockholm, Sweden
Investigational Site Number 756102
šØšOlten, Switzerland
Investigational Site Number 756103
šØšReinach, Switzerland
Investigational Site Number 792105
š¹š·Adana, Turkey
Investigational Site Number 756101
šØšGenĆØve, Switzerland
Investigational Site Number 792110
š¹š·Izmir, Turkey
Investigational Site Number 792109
š¹š·Hatay, Turkey
Investigational Site Number 792104
š¹š·Izmir, Turkey
Investigational Site Number 792101
š¹š·Izmir, Turkey
Investigational Site Number 792107
š¹š·Kayseri, Turkey
Investigational Site Number 784101
š¦šŖDubai, United Arab Emirates
Investigational Site Number 826106
š¬š§Manchester, United Kingdom
Investigational Site Number 826105
š¬š§Middlesborough, United Kingdom
Investigational Site Number 826101
š¬š§Torquay, United Kingdom
Investigational Site Number 840-178
šŗšøAlbany, New York, United States
Investigational Site Number 376106
š®š±Tel-Aviv, Israel
Investigational Site Number 840-126
šŗšøChesapeake, Virginia, United States
Investigational Site Number 840-185
šŗšøOrem, Utah, United States
Investigational Site Number 276104
š©šŖDippoldiswalde, Germany
Investigational Site Number 840-123
šŗšøTampa, Florida, United States
Investigational Site Number 840-108
šŗšøLouisville, Kentucky, United States
Investigational Site Number 840-148
šŗšøOmaha, Nebraska, United States
Investigational Site Number 840-171
šŗšøRichmond, Virginia, United States