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)

Sanofi

Status and phase: Completed; Phase 3

Conditions: Hypercholesterolaemia

Treatments: Drug: Lipid-Modifying Therapy (LMT); Drug: Alirocumab; Drug: Placebo; Drug: Antihyperglycemic Drug

Study type: Interventional

Funder types: Industry

Identifiers

NCT02585778

2015-000799-92 (EudraCT Number)

LPS14355

U1111-1172-4772 (Other Identifier)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 517 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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) <15 mL/min/1.73 m² according to the Modification of Diet in Renal Disease (MDRD) equation
• Currently received or planned to receive renal replacement therapy (for example, hemodialysis)
• Change in weight of more than 5 kilograms within the prior 2 months
• Not on a stable dose/regimen of insulin or other antidiabetic drugs for the past 3 months or planned to intensify insulin regimen during the study
• Not treated with insulin for at least 6 months
• Planned to start new lipid modifying therapy or change dose of current lipid modifying therapy during the study
• Body mass index (BMI) >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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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517 participants in 2 patient groups, including a placebo group

Alirocumab 75 mg Q2W/Up to 150 mg Q2W

Experimental group

Description:

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.

Treatment:

Drug: Antihyperglycemic Drug

Drug: Lipid-Modifying Therapy (LMT)

Drug: Alirocumab

Placebo Q2W

Placebo Comparator group

Description:

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.

Treatment:

Drug: Antihyperglycemic Drug

Drug: Placebo

Drug: Lipid-Modifying Therapy (LMT)