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

Hypercholesterolemia Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Ascending Single-Dose Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneously Administered SAR236553 in Japanese Healthy Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01448317
• Other study ID #: TDU12190
• Secondary ID: U1111-1118-1213
• Status: Completed
• Phase: Phase 1
• First received: September 21, 2011
• Last updated: September 27, 2016
• Start date: May 2011
• Est. completion date: January 2012

Study information

• Verified date: September 2016
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• Alirocumab (Solution)
Pharmaceutical form: solution Route of administration: subcutaneous
• Alirocumab (Lyophilized formulation)
Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous
• Placebo (Solution)
Pharmaceutical form: solution Route of administration: subcutaneous
• Placebo (Lyophilized formulation)
Pharmaceutical form: lyophilized formulation Route of administration: Subcutaneous

Locations

Country	Name	City	State
Japan	Sanofi-Aventis Administrative Office	Tokyo

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Country where clinical trial is conducted

Japan, 

References & Publications (1)

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.2016.04.01 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse Events		106 days	Yes
Secondary	Change in serum Low-Density Lipoprotein Cholesterol (LDL-C) from baseline to each visit.		106 days	No
Secondary	Change in ApolipoproteinB, ApolipoproteinA1 and Lipoprotein(a) from baseline to each visit.		106 days	No
Secondary	Change in Total Cholesterol (T-C), High-Density Lipoprotein Cholesterol (HDL-C), Very Low-Density Lipoprotein Cholesterol (VLDL-C) and Triglycerides (TG) from baseline to each visit.		106 days	No