Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe in Patients With Hypercholesterolemia

NCT ID: NCT01644474

Last Updated: 2015-11-06

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

103 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-07-31

Study Completion Date

2013-07-31

Brief Summary

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Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9).

Primary Objective of the study:

To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab in comparison with ezetimibe after 24 weeks of treatment in participants with hypercholesterolemia.

Secondary Objectives:

* To evaluate the effect of alirocumab in comparison with ezetimibe on LDL-C at other time points
* To evaluate the effect of alirocumab on other lipid parameters
* To evaluate the safety and tolerability of alirocumab

Detailed Description

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The maximum study duration was 34 weeks per participant, including a 24-week randomized treatment period.

Conditions

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Hypercholesterolemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Ezetimibe 10 mg

Oral ezetimibe 10 mg capsule daily and subcutaneous (SC) placebo injection for alirocumab every 2 weeks (Q2W) for 24 weeks.

Group Type ACTIVE_COMPARATOR

Ezetimibe

Intervention Type DRUG

One over-encapsulated tablet orally once daily at approximately the same time of the day with or without food.

Placebo (for Alirocumab)

Intervention Type DRUG

1 mL subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self--injection or by another designated person using the autoinjector.

Alirocumab 75/Up to 150 mg Q2W

SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.

Group Type EXPERIMENTAL

Alirocumab

Intervention Type DRUG

1 mL subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using the autoinjector.

Placebo (for Ezetimibe)

Intervention Type DRUG

One capsule orally once daily at approximately the same time of the day with or without food..

Interventions

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Alirocumab

1 mL subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using the autoinjector.

Intervention Type DRUG

Ezetimibe

One over-encapsulated tablet orally once daily at approximately the same time of the day with or without food.

Intervention Type DRUG

Placebo (for Alirocumab)

1 mL subcutaneous injection in the abdomen, thigh, or outer area of the upper arm by self--injection or by another designated person using the autoinjector.

Intervention Type DRUG

Placebo (for Ezetimibe)

One capsule orally once daily at approximately the same time of the day with or without food..

Intervention Type DRUG

Other Intervention Names

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SAR236553 REGN727

Eligibility Criteria

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Inclusion Criteria

* Participants with hypercholesterolemia

Exclusion Criteria

* Age \< 18 or legal age of adulthood, whichever was greater
* LDL-C \< 100 mg/dL (\< 2.59 mmol/L) or \> 190 mg/dL (\> 4.9 mmol/L)
* Fasting serum triglycerides (TG) \> 400 mg/dL (\> 4.52 mmol/L)
* Known history of homozygous or heterozygous familial hypercholesterolemia

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Sanofi

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

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Investigational Site Number 840603

Overland Park, Kansas, United States

Site Status

Investigational Site Number 840601

Cincinnati, Ohio, United States

Site Status

Investigational Site Number 840602

Richmond, Virginia, United States

Site Status

Investigational Site Number 056601

Antwerp, , Belgium

Site Status

Investigational Site Number 246601

Helsinki, , Finland

Site Status

Investigational Site Number 528602

Groningen, , Netherlands

Site Status

Investigational Site Number 528601

Rotterdam, , Netherlands

Site Status

Investigational Site Number 528603

Velp, , Netherlands

Site Status

Countries

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United States Belgium Finland Netherlands

References

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Roth EM, Taskinen MR, Ginsberg HN, Kastelein JJ, Colhoun HM, Robinson JG, Merlet L, Pordy R, Baccara-Dinet MT. Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial. Int J Cardiol. 2014 Sep;176(1):55-61. doi: 10.1016/j.ijcard.2014.06.049. Epub 2014 Jul 2.

Reference Type RESULT
PMID: 25037695 (View on PubMed)

Roth EM, McKenney JM. ODYSSEY MONO: effect of alirocumab 75 mg subcutaneously every 2 weeks as monotherapy versus ezetimibe over 24 weeks. Future Cardiol. 2015;11(1):27-37. doi: 10.2217/fca.14.82.

Reference Type RESULT
PMID: 25606700 (View on PubMed)

Mahmood T, Minnier J, Ito MK, Li QH, Koren A, Kam IW, Fazio S, Shapiro MD. Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies. Eur J Prev Cardiol. 2021 Jul 23;28(8):816-822. doi: 10.1177/2047487320915803. Epub 2020 Apr 10.

Reference Type DERIVED
PMID: 34298554 (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)

Ray KK, Ginsberg HN, Davidson MH, Pordy R, Bessac L, Minini P, Eckel RH, Cannon CP. Reductions in Atherogenic Lipids and Major Cardiovascular Events: A Pooled Analysis of 10 ODYSSEY Trials Comparing Alirocumab With Control. Circulation. 2016 Dec 13;134(24):1931-1943. doi: 10.1161/CIRCULATIONAHA.116.024604. Epub 2016 Oct 24.

Reference Type DERIVED
PMID: 27777279 (View on PubMed)

Other Identifiers

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U1111-1124-1167

Identifier Type: OTHER

Identifier Source: secondary_id

2011-001424-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC11716

Identifier Type: -

Identifier Source: org_study_id

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