NCT01288469

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
92

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jan 2011

Shorter than P25 for phase_2

Geographic Reach
1 country

20 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2011

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

February 1, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 2, 2011

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2011

Completed
4.1 years until next milestone

Results Posted

Study results publicly available

September 24, 2015

Completed
Last Updated

September 24, 2015

Status Verified

January 1, 2015

Enrollment Period

8 months

First QC Date

February 1, 2011

Results QC Date

August 21, 2015

Last Update Submit

August 21, 2015

Conditions

Hypercholesterolemia

Keywords

10020603

Outcome Measures

Primary Outcomes (1)

  • Percent Change From Baseline in Calculated LDL-C at Week 8 - On-treatment Analysis

    Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first investigational product (IP) injection up to 21 days after last IP injection (on-treatment analysis). Missing Week 8 data were imputed by last observation carried forward \[LOCF\] method.

    From Baseline to Week 8 (LOCF)

Secondary Outcomes (6)

  • Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 8 - On-treatment Analysis

    From baseline to Week 8 (LOCF)

  • Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 8 - On-treatment Analysis

    From baseline to Week 8 (LOCF)

  • Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and < 70 mg/dL (1.81 mmol/L) at Week 8 - On-treatment Analysis

    Week 8 (LOCF)

  • Percent Change From Baseline in Total Cholesterol, Fasting Triglycerides, Non-high-Density Lipoprotein Cholesterol (Non-HDL-C), Apolipoprotein B (Apo-B) and Lipoprotein(a) at Week 8 - On-treatment Analysis

    From baseline to Week 8 (LOCF)

  • Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 8 - On-treatment Analysis

    From Baseline to Week 8 (LOCF)

  • +1 more secondary outcomes

Study Arms (3)

Placebo + Atorvastatin 80 mg

PLACEBO COMPARATOR

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

Drug: Placebo (for alirocumab)Drug: Atorvastatin

Alirocumab + Atorvastatin 10 mg

EXPERIMENTAL

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

Drug: AlirocumabDrug: AtorvastatinDrug: Placebo (for atorvastatin)

Alirocumab + Atorvastatin 80 mg

EXPERIMENTAL

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

Drug: AlirocumabDrug: Atorvastatin

Interventions

AlirocumabDRUG

One subcutaneous (SC) injection in the abdomen only.

Also known as: SAR236553, REGN727
Alirocumab + Atorvastatin 10 mgAlirocumab + Atorvastatin 80 mg
Placebo (for alirocumab)DRUG

One SC injection in the abdomen only.

Placebo + Atorvastatin 80 mg
AtorvastatinDRUG

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

Alirocumab + Atorvastatin 10 mgAlirocumab + Atorvastatin 80 mgPlacebo + Atorvastatin 80 mg
Placebo (for atorvastatin)DRUG

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

Alirocumab + Atorvastatin 10 mg

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \- 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
  • \- 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.

You may not qualify if:

  • 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.
  • 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.
  • Participants not previously instructed on a cholesterol-lowering diet.
  • Participants with type 1 diabetes.
  • Participants with type 2 diabetes treated with insulin.
  • Participants with type 2 diabetes and with an HbA1c ≥ 8.5% at screening visit (considered poorly controlled).
  • 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.
  • Pregnant or breast-feeding women.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (20)

Investigational Site Number 840616

Mesa, Arizona, 85206, United States

Location

Investigational Site Number 840601

Tucson, Arizona, 85710, United States

Location

Investigational Site Number 840610

Los Angeles, California, 90057, United States

Location

Investigational Site Number 840608

Newport Beach, California, 92660, United States

Location

Investigational Site Number 840603

Doral, Florida, 33166, United States

Location

Investigational Site Number 840611

Jacksonville, Florida, 32223, United States

Location

Investigational Site Number 840618

Jupiter, Florida, 33458, United States

Location

Investigational Site Number 840612

Miami, Florida, 33138, United States

Location

Investigational Site Number 840614

Miami, Florida, 33138, United States

Location

Investigational Site Number 840607

St. Petersburg, Florida, 33609, United States

Location

Investigational Site Number 840605

Chicago, Illinois, 60610, United States

Location

Investigational Site Number 840619

Chicago, Illinois, 60610, United States

Location

Investigational Site Number 840604

Edison, New Jersey, 08817, United States

Location

Investigational Site Number 840606

Rochester, New York, 14609, United States

Location

Investigational Site Number 840615

Cincinnati, Ohio, 45219, United States

Location

Investigational Site Number 840617

Cincinnati, Ohio, 45219, United States

Location

Investigational Site Number 840602

Eugene, Oregon, 97404, United States

Location

Investigational Site Number 840621

Richmond, Virginia, 23227, United States

Location

Investigational Site Number 840609

Olympia, Washington, 98502, United States

Location

Investigational Site Number 840613

Oregon, Wisconsin, 53575, United States

Location

Related Publications (4)

  • 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.

    PMID: 23113833RESULT

  • 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.

    PMID: 25060413RESULT

  • 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.

    PMID: 30183102DERIVED

  • 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.

    PMID: 26872608DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

alirocumabAtorvastatin

Condition Hierarchy (Ancestors)

HyperlipidemiasDyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

PyrrolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHeptanoic AcidsFatty AcidsLipids

Results Point of Contact

Title
Trial Transparency Team
Organization
Sanofi
Contact --US@sanofi.com

Study Officials

  • Clinical Sciences & Operations

    Sanofi

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 1, 2011

First Posted

February 2, 2011

Study Start

January 1, 2011

Primary Completion

September 1, 2011

Study Completion

September 1, 2011

Last Updated

September 24, 2015

Results First Posted

September 24, 2015

Record last verified: 2015-01

Locations

US(20)