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

NCT ID: NCT01288469

Last Updated: 2015-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2011-09-30

Brief Summary

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.

Detailed 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.

Conditions

Hypercholesterolemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo + Atorvastatin 80 mg

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

Group Type: PLACEBO_COMPARATOR

Placebo (for alirocumab)

Intervention Type: DRUG

One SC injection in the abdomen only.

Atorvastatin

Intervention Type: DRUG

Over-encapsulated tablet orally once daily in the evening with dinner.

Alirocumab + Atorvastatin 10 mg

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

Group Type: EXPERIMENTAL

Alirocumab

Intervention Type: DRUG

One subcutaneous (SC) injection in the abdomen only.

Atorvastatin

Intervention Type: DRUG

Over-encapsulated tablet orally once daily in the evening with dinner.

Placebo (for atorvastatin)

Intervention Type: DRUG

One over-encapsulated tablet of placebo for atorvastatin orally once daily in the evening with dinner.

Alirocumab + Atorvastatin 80 mg

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

Group Type: EXPERIMENTAL

Alirocumab

Intervention Type: DRUG

One subcutaneous (SC) injection in the abdomen only.

Atorvastatin

Intervention Type: DRUG

Over-encapsulated tablet orally once daily in the evening with dinner.

Interventions

Alirocumab

One subcutaneous (SC) injection in the abdomen only.

Intervention Type: DRUG

Placebo (for alirocumab)

One SC injection in the abdomen only.

Intervention Type: DRUG

Atorvastatin

Over-encapsulated tablet orally once daily in the evening with dinner.

Intervention Type: DRUG

Placebo (for atorvastatin)

One over-encapsulated tablet of placebo for atorvastatin orally once daily in the evening with dinner.

Intervention Type: DRUG

Other Intervention Names

SAR236553; REGN727

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840616

Mesa, Arizona, United States

Investigational Site Number 840601

Tucson, Arizona, United States

Investigational Site Number 840610

Los Angeles, California, United States

Investigational Site Number 840608

Newport Beach, California, United States

Investigational Site Number 840603

Doral, Florida, United States

Investigational Site Number 840611

Jacksonville, Florida, United States

Investigational Site Number 840618

Jupiter, Florida, United States

Investigational Site Number 840612

Miami, Florida, United States

Investigational Site Number 840614

Miami, Florida, United States

Investigational Site Number 840607

St. Petersburg, Florida, United States

Investigational Site Number 840605

Chicago, Illinois, United States

Investigational Site Number 840619

Chicago, Illinois, United States

Investigational Site Number 840604

Edison, New Jersey, United States

Investigational Site Number 840606

Rochester, New York, United States

Investigational Site Number 840615

Cincinnati, Ohio, United States

Investigational Site Number 840617

Cincinnati, Ohio, United States

Investigational Site Number 840602

Eugene, Oregon, United States

Investigational Site Number 840621

Richmond, Virginia, United States

Investigational Site Number 840609

Olympia, Washington, United States

Investigational Site Number 840613

Oregon, Wisconsin, United States

Countries

United States

References

Roth EM, McKenney JM, Hanotin C, Asset G, Stein EA. Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N Engl J Med. 2012 Nov 15;367(20):1891-900. doi: 10.1056/NEJMoa1201832. Epub 2012 Oct 31.

Reference Type: RESULT

PMID: 23113833 (View on PubMed)

Gaudet D, Kereiakes DJ, McKenney JM, Roth EM, Hanotin C, Gipe D, Du Y, Ferrand AC, Ginsberg HN, Stein EA. Effect of alirocumab, a monoclonal proprotein convertase subtilisin/kexin 9 antibody, on lipoprotein(a) concentrations (a pooled analysis of 150 mg every two weeks dosing from phase 2 trials). Am J Cardiol. 2014 Sep 1;114(5):711-5. doi: 10.1016/j.amjcard.2014.05.060. Epub 2014 Jun 18.

Reference Type: RESULT

PMID: 25060413 (View on PubMed)

Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.

Reference Type: DERIVED

PMID: 30183102 (View on PubMed)

Toth PP, Hamon SC, Jones SR, Martin SS, Joshi PH, Kulkarni KR, Banerjee P, Hanotin C, Roth EM, McKenney JM. Effect of alirocumab on specific lipoprotein non-high-density lipoprotein cholesterol and subfractions as measured by the vertical auto profile method: analysis of 3 randomized trials versus placebo. Lipids Health Dis. 2016 Feb 13;15:28. doi: 10.1186/s12944-016-0197-4.

Reference Type: DERIVED

PMID: 26872608 (View on PubMed)

Other Identifiers

U1111-1117-9994

Identifier Type: OTHER

Identifier Source: secondary_id

DFI11566

Identifier Type: -

Identifier Source: org_study_id