Phase 4
Completed N=413
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)
Source: ClinicalTrials.gov NCT02642159 ↗Enrolled (actual)
413
Serious AEs
9.2%
Results posted
May 2018
Primary outcomePrimary: Percent Change From Baseline in Non-HDL-C at Week 24: Overall Intent-to-treat (ITT) Analysis — -37.3; -4.7 Percent change — p=<0.0001
◆ Published Evidence
Highly cited
126citations · ~21 / year
PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease.
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).
Linked Publications (5)
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PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease.
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Alirocumab vs usual lipid-lowering care as add-on to statin therapy in individuals with type 2 diabetes and mixed dyslipidaemia: The ODYSSEY DM-DYSLIPIDEMIA randomized trial.
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Alirocumab therapy in individuals with type 2 diabetes mellitus and atherosclerotic cardiovascular disease: analysis of the ODYSSEY DM-DYSLIPIDEMIA and DM-INSULIN studies.
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Effect of alirocumab on individuals with type 2 diabetes, high triglycerides, and low high-density lipoprotein cholesterol.
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Design and rationale of the ODYSSEY DM-DYSLIPIDEMIA trial: lipid-lowering efficacy and safety of alirocumab in individuals with type 2 diabetes and mixed dyslipidaemia at high cardiovascular risk.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Non-HDL-C at Week 24: Overall Intent-to-treat (ITT) Analysis |
-37.3; -4.7 | <0.0001 sig |
| PRIMARY Percent Change From Baseline in Non-HDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum |
-41.7; -8.5 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Measured Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24: Overall ITT Analysis |
-43.3; -0.3 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Measured LDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum |
-47.0; 8.7 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Non-HDL-C at Week 12: Overall ITT Analysis |
-35.5; -9.4 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Non-HDL-C at Week 12: ITT- Intent to Prescribe Fenofibrate Stratum |
-34.7; -7.3 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Measured LDL-C at Week 12: Overall ITT Analysis |
-41.7; -7.0 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Measured LDL-C at Week 12: ITT- Intent to Prescribe Fenofibrate Stratum |
-44.3; 5.4 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24: Overall ITT Analysis |
-33.8; -1.6 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Apo B at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum |
-38.9; -3.8 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 : Overall ITT Analysis |
-27.4; -2.8 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Total-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum |
-30.9; -5.7 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Lipoprotein(a) at Week 24 : Overall ITT Analysis |
-23.7; 3.7 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Lipoprotein(a) at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum |
-18.9; 3.9 | 0.0040 sig |
| SECONDARY Percent Change From Baseline in Fasting Triglycerides at Week 24: Overall ITT Analysis |
-13.0; -8.8 | 0.2191 |
| SECONDARY Percent Change From Baseline in Fasting Triglycerides at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum |
-15.4; -24.4 | 0.2651 |
| SECONDARY Percent Change From Baseline in HDL-C at Week 24 : Overall ITT Analysis |
14.5; 8.2 | — |
| SECONDARY Percent Change From Baseline in HDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum |
13.5; 12.3 | — |
| SECONDARY Percent Change From Baseline in LDL-C Particle Number at Week 24: Overall ITT Analysis |
-41.6; -3.9 | — |
| SECONDARY Percent Change From Baseline in LDL-C Particle Number at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum |
-45.4; -2.9 | — |
| SECONDARY Absolute Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 and 24 : Overall ITT Analysis |
0.59; 0.43; 2.84; 2.40 | — |
| SECONDARY Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 and 24 : Overall ITT Analysis |
0.45; 0.21; 0.68; 0.03 | — |
| SECONDARY Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Week 12 and 24 : Overall ITT Analysis |
0.04; 0.04; 0.07; 0.04 | — |
Eligibility Criteria
Inclusion criteria
- Participants with type 2 diabetes and mixed dyslipidemia whose non-HDL-C was not adequately controlled with a stable, maximum dose/regimen of statin that was tolerated by the participant.
- 18 years of age or more.
- Documented history of atherosclerotic cardiovascular disease (ASCVD) or at least one additional cardiovascular risk factor.
- Non-HDL-C of 100 mg/dL or greater.
- Triglycerides greater than or equal to 150 mg/dL and less than 500 mg/dL.
- Stable anti-hyperglycemic agents for at least 3 months prior to the screening visit and between screening and randomization (including stable insulin dose defined as no variation more than 30% in daily insulin dose within the preceding 3 months, as judged by the Investigator).
- No change in weight of more than 5 kg within the prior 3 months.
- On stable dose of medications that are known to influence weight and/or lipids within the last 3 months.
Exclusion criteria
- Use of any lipid modifying therapies other than statins within the last 4 weeks (eg, ezetimibe, fenofibrate, nicotinic acid, omega-3 fatty acids, etc.) or use of over the counter products/nutraceuticals known to impact lipids (eg, red yeast rice) within the last 4 weeks.
- Currently drinking more than 2 standard alcoholic drinks per day.
- Body Mass Index (BMI) >45 kg/m² or currently enrolled in a weight loss program and still in active phase of weight loss.
- Glycosylated hemoglobin (HbA1c) 9% or greater.
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Data sourced from ClinicalTrials.gov (NCT02642159) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.