Phase 3
N=517
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)
Hypercholesterolaemia
Bottom Line
View on ClinicalTrials.gov: NCT02585778 ↗Enrolled (actual)
517
Serious AEs
9.1%
Results posted
May 2018
Primary outcome: Primary: Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis — -51.8; -3.9; -48.2; 0.8 percent change — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Alirocumab (Drug); Placebo (Drug); Lipid-Modifying Therapy (LMT) (Drug); Antihyperglycemic Drug (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Sanofi
- Primary completion
- Apr 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis |
-51.8; -3.9; -48.2; 0.8 | <0.0001 sig |
| PRIMARY Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) |
64.5; 64.1; 9.0; 9.4; 0; 0.6 | — |
| SECONDARY Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis |
-53.8; -3.2; -50.9; 0.7 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis |
-49.4; -1.1; -43.3; 2.4 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis |
-49.4; -4.5; -48.8; 1.4 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Measured LDL-C at Week 12 - ITT Analysis |
-46.7; -4.0; -44.8; -0.8 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis |
-45.9; -3.2; -37.9; 0.7 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24 - ITT Analysis |
-39.4; -0.4; -33.4; 3.3 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis |
-29.9; -0.7; -26.8; 0.8 | <0.0001 sig |
| SECONDARY Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis |
70.2; 5.1; 76.4; 7.4 | <0.0001 sig |
| SECONDARY Percentage of Participants Reaching Calculated LDL-C <50 mg/dL (1.3 mmol/L) at Week 24 - On-Treatment Analysis |
55.1; 0; 50.7; 2.7 | <0.0001 sig |
| SECONDARY Percentage of Participants Reaching Calculated Non-HDL-C <100 mg/dL at Week 24 - On-Treatment Analysis |
79.0; 22.9; 70.9; 13.8 | <0.0001 sig |
| SECONDARY Percentage of Participants Reaching Calculated Non-HDL-C <80 mg/dL at Week 24 - On-Treatment Analysis |
59.6; 5.3; 52.3; 1.7 | 0.0002 sig |
| SECONDARY Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis |
-23.0; -4.3; -19.0; -0.5 | 0.0039 sig |
| SECONDARY Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis |
11.2; 7.3; 8.1; 3.7 | 0.3434 |
| SECONDARY Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis |
-13.6; 1.9; -5.7; 0.0 | 0.0902 |
| SECONDARY Percent Change From Baseline in LDL-C Particle Number at Week 24 - ITT Analysis |
-44.4; -4.4; -38.3; 1.9 | — |
| SECONDARY Percent Change From Baseline in LDL-C Particle Size at Week 24 - ITT Analysis |
-2.3; 0.8; -2.8; -0.3 | — |
| SECONDARY Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24 - ITT Analysis |
0.00; -0.22; -0.04; 0.00; -0.03; -0.23 | — |
| SECONDARY Absolute Change From Baseline in HbA1c at Weeks 12 and 24 - On-Treatment Analysis |
0.00; -0.22; -0.04; 0.00; -0.05; -0.27 | — |
| SECONDARY Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 12 and 24 - ITT Analysis |
0.23; 0.45; 0.25; 0.13; 0.52; 0.81 | — |
| SECONDARY Absolute Change From Baseline in FPG at Weeks 12 and 24 - On-Treatment Analysis |
0.23; 0.45; 0.22; 0.15; 0.38; 0.71 | — |
| SECONDARY Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - ITT Analysis |
-10.0; -1.3; 0.2; 1.4; -2.2; -0.8 | — |
| SECONDARY Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - On-Treatment Analysis |
-10.0; -1.3; 0.2; 1.4; -2.2; -0.8 | — |
| SECONDARY Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - ITT Analysis |
-0.1; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - On-Treatment Analysis |
-0.1; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - ITT Analysis |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - On-Treatment Analysis |
0; 0; 0; 0; 0; 0 | — |
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).
Eligibility Criteria
Inclusion criteria
- Participants diagnosed with Type 1 or Type 2 diabetes at least one year prior to the screening visit (Week -3).
- Signed written informed consent
- Participants with type 1 or type 2 diabetes treated with insulin whose LDL-C levels were not adequately controlled with maximally tolerated lipid-modifying therapy
- LDL-C of 70 mg/dL or greater
- 18 years of age or more
- Glycosylated hemoglobin (HbA1c) less than 10%
- History of cardiovascular disease (including coronary heart disease [CHD] and/or CHD risk equivalents) and/or at least one additional cardiovascular risk factor
Exclusion criteria
- Not on a stable dose of statin or other lipid modifying therapy for at least 4 weeks prior to screening or from screening to randomization, unless statin intolerant
- Triglycerides >400 mg/dL
- Estimated glomerular filtration rate (eGFR) 45 kg/m² or planned to undergo bariatric surgery, weight loss program, or initiate weight loss drugs during the study
- History of recent decompensation of diabetes within the prior 2 months (for example, diabetic ketoacidosis)
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 (NCT02585778). 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.