Ascending Dose Study of the Safety and Tolerability of Alirocumab (SAR236553/REGN727) in Japanese Healthy Volunteers

NCT ID: NCT01448317

Last Updated: 2016-09-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2012-01-31

Brief Summary

Primary Objective:

To assess the safety and tolerability of ascending single doses of subcutaneously (SC) administered alirocumab (SAR236553/REGN727) in Japanese healthy male subjects.

Secondary Objectives:

• To assess the pharmacodynamics effect of a single SC dose of alirocumab on serum low-density lipoprotein cholesterol (LDL-C) and other lipids and apolipoproteins such as total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, Triglycerides, Apolipoprotein B, Apolipoprotein A1 and Lipoprotein(a).
• To assess the Pharmacokinetic profile of a single SC dose of alirocumab.
• To assess the immunogenicity of a single SC dose of alirocumab.

Detailed Description

4 sequential dose cohorts. Single dose followed by a total observation period of 15 weeks (106 days) for each participant.

Conditions

Hypercholesterolemia

Study Design

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

Study Groups

Cohort 1

Alirocumab dose 1 versus placebo

Group Type: EXPERIMENTAL

Alirocumab (Lyophilized formulation)

Intervention Type: DRUG

Pharmaceutical form: lyophilized formulation

Route of administration: subcutaneous

Placebo (Lyophilized formulation)

Intervention Type: DRUG

Pharmaceutical form: lyophilized formulation

Route of administration: Subcutaneous

Cohort 2

Alirocumab dose 2 versus placebo

Group Type: EXPERIMENTAL

Alirocumab (Lyophilized formulation)

Intervention Type: DRUG

Pharmaceutical form: lyophilized formulation

Route of administration: subcutaneous

Placebo (Lyophilized formulation)

Intervention Type: DRUG

Pharmaceutical form: lyophilized formulation

Route of administration: Subcutaneous

Cohort 3

Alirocumab dose 3 versus placebo

Group Type: EXPERIMENTAL

Alirocumab (Lyophilized formulation)

Intervention Type: DRUG

Pharmaceutical form: lyophilized formulation

Route of administration: subcutaneous

Placebo (Lyophilized formulation)

Intervention Type: DRUG

Pharmaceutical form: lyophilized formulation

Route of administration: Subcutaneous

Cohort 4

Alirocumab dose 4 versus placebo

Group Type: EXPERIMENTAL

Alirocumab (Solution)

Intervention Type: DRUG

Pharmaceutical form: solution

Route of administration: subcutaneous

Placebo (Solution)

Intervention Type: DRUG

Pharmaceutical form: solution

Route of administration: subcutaneous

Interventions

Alirocumab (Solution)

Pharmaceutical form: solution

Route of administration: subcutaneous

Intervention Type: DRUG

Alirocumab (Lyophilized formulation)

Pharmaceutical form: lyophilized formulation

Route of administration: subcutaneous

Intervention Type: DRUG

Placebo (Solution)

Pharmaceutical form: solution

Route of administration: subcutaneous

Intervention Type: DRUG

Placebo (Lyophilized formulation)

Pharmaceutical form: lyophilized formulation

Route of administration: Subcutaneous

Intervention Type: DRUG

Other Intervention Names

SAR236553; REGN727; SAR236553; REGN727

Eligibility Criteria

Inclusion Criteria

• Healthy male subject, between 20 and 65 years inclusive.
• Body weight between 50.0 and 95.0 kg inclusive, body mass index between 18.0 and 30.0 kg/m² inclusive.
• Serum LDL-C levels >100 mg/dL

Exclusion Criteria

• Subject indicated for the use of statins according to criteria in Adult Treatment Panel (ATP) III Guidelines as updated in 2004
• Significant concomitant illness or history of significant illness such as cardiac, renal, neurological, endocrinological, dermatological, metabolic or lymphatic disease, or any other illness or condition that would adversely affect the subject's participation in this study.
• History or presence of drug or alcohol abuse
• Smoking more than 5 cigarettes or equivalent in any 24 hour period.
• Any medication (including St John's Wort) within 14 days before the inclusion or within 5 times the elimination half-life or pharmacodynamic (PD) half-life of that drug, whichever the longest; any vaccination within the last 28 days.
• Positive reaction to any of the following tests: hepatitis B surface (HBs Ag) antigen, anti-hepatitis B core antibodies (anti-HBc Ab), anti-hepatitis C virus (anti-HCV) antibodies, human immunodeficiency virus (HIV) antigen and antibodies, syphilis.
• Elevated cholesterol due to a secondary cause such as hypothyroidism or alcohol.
• Presence or history of drug hypersensitivity
• Initiation of a new exercise routine or major change to a previous exercise routine within 4 weeks prior to Screening.
• Initiation of a new diet or major change to a previous diet within 4 weeks prior to Screening.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

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

Sanofi-Aventis Administrative Office

Tokyo, , Japan

Countries

Japan

References

Teramoto T, Kobayashi M, Uno K, Takagi Y, Matsuoka O, Sugimoto M, Inoue S, Minami F, Baccara-Dinet MT. Efficacy and Safety of Alirocumab in Japanese Subjects (Phase 1 and 2 Studies). Am J Cardiol. 2016 Jul 1;118(1):56-63. doi: 10.1016/j.amjcard.2016.04.011. Epub 2016 Apr 21.

Reference Type: RESULT

PMID: 27184170 (View on PubMed)

Other Identifiers

U1111-1118-1213

Identifier Type: OTHER

Identifier Source: secondary_id

TDU12190

Identifier Type: -

Identifier Source: org_study_id