Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) When Co-administered With High Dose of Atorvastatin in Patients With Primary Hypercholesterolemia

Sanofi

Status and phase: Completed; Phase 2

Conditions: Hypercholesterolemia

Treatments: Drug: Atorvastatin; Drug: Alirocumab; Drug: Placebo (for alirocumab); Drug: Placebo (for atorvastatin)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01288469

U1111-1117-9994 (Other Identifier)

DFI11566

Details and patient eligibility

About

Primary Objective:

To evaluate the effect of alirocumab (SAR236553/REGN727) on low-density lipoprotein cholesterol (LDL-C) levels compared with placebo when co-administered with 80 mg of atorvastatin after 8 weeks of treatment in participants with LDL-C ≥ 100mg/dL (≥ 2.59 mmol/L) on atorvastatin 10 mg.

Secondary Objectives:

• To evaluate the effects of alirocumab on other lipid levels in comparison with placebo, when co-administered with 80 mg of atorvastatin after 8 weeks of treatment.
• To evaluate the efficacy of alirocumab when co-administered with a high dose of atorvastatin (80 mg) versus atorvastatin 10 mg.
• To evaluate the safety and tolerability of alirocumab when co-administered with 2 different doses of atorvastatin.
• To evaluate the development of anti-alirocumab antibodies.
• To evaluate the pharmacokinetics of alirocumab.

Full description

The duration of study participation depended on the status of the patient at screening:

• For participants receiving atorvastatin 10 mg at stable dose for at least 6 weeks prior to screening, the study participation was to be approximately 17 weeks including a screening period of 1 week, a double-blind treatment period of 8 weeks and a follow-up period of 8 weeks.
• For participants receiving a lipid lowering treatment other than atorvastatin/ or not at stable dose of atorvastatin 10 mg for at least 6 weeks prior to screening, or drug naive participants, the study participation was to be approximately 23 weeks with a screening period of 1 week, a run-in treatment period with atorvastatin 10 mg of 6 weeks, a double-blind treatment period of 8 weeks and a follow-up period of 8 weeks.

Enrollment: 92 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants receiving a lipid-lowering treatment other than atorvastatin/ or not at stable dose of atorvastatin 10 mg for at least 6 weeks prior to screening, or drug naive participants with primary hypercholesterolemia if they are likely to have low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥ 2.59 mmol/L) at the end of the 6-week run-in treatment period on atorvastatin therapy

OR

• Participants with primary hypercholesterolemia treated with stable dose of atorvastatin 10 mg for at least 6 weeks prior to screening and likely to have low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (≥ 2.59 mmol/L) at the screening visit.

Exclusion criteria

1. LDL-C < 100 mg/dL (< 2.59 mmol/L) at Week -1 (V1):

   • After the run-in period on atorvastatin 10 mg for participants receiving a lipid lowering treatment other than atorvastatin/ or not at stable dose of atorvastatin 10 mg for at least 6 weeks prior to the screening period, or drug naive participants.

   OR

   • At the first visit for participants who are being treated with atorvastatin 10 mg at stable dose for at least 6 weeks prior to screening visit.

2. Participants not previously instructed on a cholesterol-lowering diet.

3. Participants with type 1 diabetes.

4. Participants with type 2 diabetes treated with insulin.

5. Participants with type 2 diabetes and with an HbA1c ≥ 8.5% at screening visit (considered poorly controlled).

6. Laboratory findings measured before randomization:

   • Triglycerides (TG) > 350 mg/dL (> 3.95 mmol/L) at screening visit.
   • Positive serum or urine pregnancy test in females of childbearing potential.

7. Pregnant or breast-feeding women.

8. Women of childbearing potential with no effective contraceptive method.

The above information is 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: Quadruple Blind

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92 participants in 3 patient groups, including a placebo group

Placebo + Atorvastatin 80 mg

Placebo Comparator group

Description:

Placebo (for alirocumab) subcutaneous (SC) administration every 2 weeks (Q2W) in combination with atorvastatin 80 mg orally once daily for 8 weeks.

Treatment:

Drug: Placebo (for alirocumab)

Drug: Atorvastatin

Alirocumab + Atorvastatin 10 mg

Experimental group

Description:

Alirocumab 150 mg SC administration Q2W in combination with atorvastatin 10 mg orally once daily for 8 weeks.

Treatment:

Drug: Alirocumab

Drug: Placebo (for atorvastatin)

Drug: Atorvastatin

Alirocumab + Atorvastatin 80 mg

Experimental group

Description:

Alirocumab 150 mg SC administration Q2W in combination with atorvastatin 80 mg orally once daily for 8 weeks.

Treatment:

Drug: Alirocumab

Drug: Atorvastatin