Study of the Efficacy and Safety of Alirocumab (REGN727/SAR236553) in Combination With Other Lipid-modifying Treatment (LMT) (ODYSSEY OPTIONS I)

Regeneron Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Hypercholesterolemia

Treatments: Drug: Atorvastatin; Drug: Alirocumab; Drug: Ezetimibe; Drug: Placebo; Drug: Rosuvastatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01730040

R727-CL-1110

Details and patient eligibility

About

This is a randomized, double-blind, active-comparator, parallel-group study in patients at high cardiovascular risk with nonfamilial hypercholesterolemia or heterozygous familial hypercholesterolemia (heFH).

Enrollment: 355 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients with screening (visit 1) LDL-C greater than or equal to 70 mg/dL with documented CVD, not adequately controlled with a daily dose of atorvastatin. OR
2. Patients with screening (visit 1) LDL-C greater than or equal to 100 mg/dL at high risk for CVD who are not adequately controlled with a daily dose of atorvastatin.

Exclusion criteria

1. LDL-C greater than 250 mg/dL
2. LDL-C less than 70 mg/dL at the screening visit in patients with history of documented CVD
3. LDL-C less than 100 mg/dL at the screening visit in patients without history of documented CHD or non-CHD CVD, but with other risk factors
4. TG greater than 400 mg/dL
5. Homozygous FH (clinically or previous genotyping)
6. Currently taking a statin that is not atorvastatin
7. Currently taking Ezetimibe (EZE)
8. Not on a stable dose of allowable lipid modifying treatments (LMT)

(The inclusion/ exclusion criteria provided above is not intended to contain all considerations relevant to a patient's potential participation in this clinical trial).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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355 participants in 7 patient groups

Atorvastatin 40 mg

Active Comparator group

Description:

Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received atorvastatin 40 mg over-encapsulated tablets orally once daily (QD), placebo for alirocumab SC injection every two weeks (Q2W), and placebo for ezetimibe over-encapsulated tablets orally QD added to stable Lipid-Modifying Therapy (LMT) for 24 weeks.

Treatment:

Drug: Placebo

Drug: Atorvastatin

Ezetimibe 10 mg + Atorvastatin 20 mg

Active Comparator group

Description:

Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.

Treatment:

Drug: Ezetimibe

Drug: Placebo

Drug: Atorvastatin

Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg

Experimental group

Description:

Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received Alirocumab 75 mg SC injection Q2W, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT 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) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.

Treatment:

Drug: Placebo

Drug: Alirocumab

Drug: Atorvastatin

Atorvastatin 80 mg

Active Comparator group

Description:

Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received Atorvastatin 80 mg over-encapsulated tablets orally QD, placebo for alirocumab SC injection Q2W, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks.

Treatment:

Drug: Placebo

Drug: Atorvastatin

Rosuvastatin 40 mg

Active Comparator group

Description:

Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received rosuvastatin 40 mg over-encapsulated tablets orally QD, placebo for alirocumab SC injection Q2W, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks.

Treatment:

Drug: Rosuvastatin

Drug: Placebo

Ezetimibe 10 mg + Atorvastatin 40 mg

Active Comparator group

Description:

Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.

Treatment:

Drug: Ezetimibe

Drug: Placebo

Drug: Atorvastatin

Alirocumab 75 mg/ up to 150 mg + Atorvastatin 40 mg

Experimental group

Description:

Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received alirocumab 75 mg SC injection Q2W, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT 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) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.

Treatment:

Drug: Placebo

Drug: Alirocumab

Drug: Atorvastatin