Pharmacokinetic and Tolerability of Alirocumab SAR236553 (REGN727) in Patients With Hepatic Impairment and in Healthy Subjects

Study Overview
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Brief Summary
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Primary Objective: Study the effect of mild or moderate hepatic impairment on the pharmacokinetics of alirocumab SAR236553 (REGN727). Secondary Objectives: Assess the safety and tolerability of alirocumab SAR236553 (REGN727) in patients with mild and moderate hepatic impairment and in matched subjects with normal hepatic function. Assess the pharmacodynamic profile of alirocumab SAR236553 (REGN727) in patients with hepatic impairment and in matched subjects with normal hepatic function.

Detailed Description
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Total duration of the study per subject (excluding screening) is about 12 weeks.

Official Title
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An Open-Label, Pharmacokinetic and Tolerability Study of SAR236553/REGN727 Given as a Single SC Dose in Subjects With Mild and Moderate Hepatic Impairment, and in Matched Subjects With Normal Hepatic Function

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: alirocumab SAR236553 (REGN727)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Male or female, between 18 to 75 years of age, inclusive. Patients with mild and moderate hepatic impairment based on Child-Pugh score and stable chronic liver disease. Healthy subjects with normal hepatic function. Exclusion criteria: Patients with acute hepatitis, hepatic encephalopathy grade 2, 3, and 4. Patients with history or presence of uncontrolled clinically relevant illness. Healthy subjects with history or presence of clinically relevant illness. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: alirocumab SAR236553 (REGN727) - mild hepatic function<br>Injection through subcutaneous (SC) administration in patients with mild hepatic function | Drug: alirocumab SAR236553 (REGN727)<br>* alirocumab SAR236553 (REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9) Pharmaceutical form:Solution for injection Route of administration: subcutaneous<br>|
| Experimental: alirocumab SAR236553 (REGN727) - moderate hepatic function<br>Injection through subcutaneous (SC) administration in patients with moderate hepatic function | Drug: alirocumab SAR236553 (REGN727)<br>* alirocumab SAR236553 (REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9) Pharmaceutical form:Solution for injection Route of administration: subcutaneous<br>|
| Experimental: alirocumab SAR236553 (REGN727) - normal hepatic function<br>Injection through subcutaneous (SC) administration in patients with normal hepatic function | Drug: alirocumab SAR236553 (REGN727)<br>* alirocumab SAR236553 (REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9) Pharmaceutical form:Solution for injection Route of administration: subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Assessment of serum concentrations of alirocumab SAR236553 (REGN727) |  | Up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of PK parameter - terminal elimination half-life (t1/2z) [ |  | Up to 12 weeks | 
| Assessment of PK parameter - apparent total body clearance (CL/F) |  | Up to 12 weeks | 
| Assessment of PK parameter - Distribution volume at the steady-state (Vss/F) |  | Up to 12 weeks | 
| Assessment of PK parameter - time to maximum concentration (tmax) |  | Up to 12 weeks | 
| Assessment of PK parameter - Mean Residence Time (MRT [area]) |  | Up to 12 weeks | 
| Pharmacodynamics: Change in LDL-C from baseline |  | Up to 12 weeks | 
| Number of participants with Adverse Events |  | Up to 12 weeks |