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

• ClinicalTrials.gov Identifier: NCT01670734
• Recruitment Status: Completed
• First Posted: August 22, 2012
• Last Update Posted: June 28, 2013
• Sponsor: Sanofi
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Sanofi

Tracking Information

• First Submitted Date: August 16, 2012
• First Posted Date: August 22, 2012
• Last Update Posted Date: June 28, 2013
• Study Start Date: September 2012
• Actual Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 27, 2013): Pharmacokinetics: Assessment of serum concentrations of alirocumab SAR236553 (REGN727) [ Time Frame: Up to 12 weeks ]
• Original Primary Outcome Measures (submitted: August 20, 2012): Pharmacokinetics: Assessment of serum concentrations of SAR236553 (REGN727) [ Time Frame: Up to 12 weeks ]

Current Secondary Outcome Measures (submitted: August 20, 2012)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pharmacokinetic and Tolerability of Alirocumab SAR236553 (REGN727) in Patients With Hepatic Impairment and in Healthy Subjects
• Official Title: 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

Brief Summary

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: Total duration of the study per subject (excluding screening) is about 12 weeks.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Hypercholesterolemia

Intervention

Drug: alirocumab SAR236553 (REGN727)

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

Study Arms

• Experimental: alirocumab SAR236553 (REGN727) - mild hepatic function
  Injection through subcutaneous (SC) administration in patients with mild hepatic function
  Intervention: Drug: alirocumab SAR236553 (REGN727)
• Experimental: alirocumab SAR236553 (REGN727) - moderate hepatic function
  Injection through subcutaneous (SC) administration in patients with moderate hepatic function
  Intervention: Drug: alirocumab SAR236553 (REGN727)
• Experimental: alirocumab SAR236553 (REGN727) - normal hepatic function
  Injection through subcutaneous (SC) administration in patients with normal hepatic function
  Intervention: Drug: alirocumab SAR236553 (REGN727)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 11, 2013): 25
• Original Estimated Enrollment (submitted: August 20, 2012): 24
• Actual Study Completion Date: May 2013
• Actual Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Moldova, Republic of

Administrative Information

• NCT Number: NCT01670734
• Other Study ID Numbers: POP12671; 2012-002292-33; U1111-1129-0248 ( Other Identifier: UTN )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sanofi
• Original Responsible Party: Same as current
• Current Study Sponsor: Sanofi
• Original Study Sponsor: Same as current
• Collaborators: Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: June 2013