Ascending Multi-dose Study of REGN727(SAR236553) With and Without Concomitant Atorvastatin

A Randomized, Double-Blind, Placebo-Controlled, Ascending Single to Multi-Dose Study of Safety, Tolerability, and Bioeffect of Subcutaneously Administered REGN727 in Patients With and Without Concomitant Atorvastatin

This study will test the safety, tolerability, and bioeffects (how the body reacts to the drug) of REGN727 compared with placebo (an inactive substance that contains no medicine) in hyperlipidemic patients with or without atorvastatin therapy. The study drug and placebo will be administered by subcutaneous injection at the clinic. There will be a total of 2 or 3 study drug injections over 16 clinic visits, which will include 3 overnight stays(study duration 148 days, not including the screening period). Patients on atorvastatin will take their daily dose in the morning for the duration of the study. Patients will be monitored by the study staff for side effects and the body's response to the study drug. Vital signs(blood pressure, temperature, breathing and heart rate) will be checked, and blood and urine samples will be collected at some or all visits.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: REGN727(SAR236553)

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States
      • Site 1
  • Tennessee
    • Knoxville, Tennessee, United States
      • Site 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Men and women with elevated cholesterol on stable doses of atorvastatin 10-40mg/day regimen
• Body mass index between 18.0 and 35.0 kg/m2, inclusive
• For women of childbearing potential, a negative serum pregnancy test at the screening visit and a negative urine pregnancy test on day -2 or day -1
• For men and women of childbearing potential, willingness to utilize adequate contraception and not become pregnant (or have their partner[s] become pregnant)during the full duration of the study
• Willing, committed and able to return for all the clinic visits and complete all study-related procedures
• Able to read, and able to sign the informed consent form

Exclusion Criteria:

• History of MI, ACS, Angina, Stroke, peripheral vascular disease, or cardiac revascularization
• Pregnant or breast-feeding women
• Blood donation of any volume within 1 month prior to administration of study drug
• Congestive heart failure
• Consumption of greater than 1 quart of grapefruit juice per day
• Previous exposure to any therapeutic or investigational biological agent within 30 days of screening
• History of alcohol or drug abuse within one year to the screening visit

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 with atorvastatin; Dose 1 versus placebo	Drug: REGN727(SAR236553); subcutaneous
Experimental: Group 2 with atorvastatin; Dose 1 versus placebo	Drug: REGN727(SAR236553); subcutaneous
Experimental: Group 3 with atorvastatin; Dose 2 versus placebo	Drug: REGN727(SAR236553); subcutaneous
Experimental: Group 4 with atorvastatin; Dose 2 versus placebo	Drug: REGN727(SAR236553); subcutaneous
Experimental: Group 5 with atorvastatin; Dose 3 versus placebo	Drug: REGN727(SAR236553); subcutaneous
Experimental: Group 6 with atorvastatin; Dose 3 versus placebo	Drug: REGN727(SAR236553); subcutaneous
Experimental: Group 7 without atorvastatin; Dose 3 versus placebo	Drug: REGN727(SAR236553); subcutaneous
Experimental: Group 8 with atorvastatin; Dose4 versus placebo	Drug: REGN727(SAR236553); subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint in the study is to assess the incidence and severity of treatment-emergent adverse events in hyperlipidemic patients treated with REGN727 or placebo receiving stable doses of atorvastatin.	visit 4 (day 1) to visit 16 (day 148)

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the pharmacodynamic effect of REGN727 added to atorvastatin on lipids	Visit 4 (Day 1) to Visit 16 (Day 148)
To assess the pharmacodynamic effect of monotherapy REGN727 in hyperlipidemic patients	Visit 4 (Day 1) to Visit 16 (Day 148)
To assess the pharmacokinetics of REGN727 in hyperlipidemic patients with or without atorvastatin	Visit 4 (Day 1) to Visit 16 (Day 148)

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi
• Investigators: Study Director: Gary Swergold, MD, PhD, Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Stein EA, Mellis S, Yancopoulos GD, Stahl N, Logan D, Smith WB, Lisbon E, Gutierrez M, Webb C, Wu R, Du Y, Kranz T, Gasparino E, Swergold GD. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med. 2012 Mar 22;366(12):1108-18. doi: 10.1056/NEJMoa1105803.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: July 9, 2010
• First Submitted That Met QC Criteria: July 9, 2010
• First Posted (Estimate): July 13, 2010

Study Record Updates

• Last Update Posted (Estimate): January 27, 2015
• Last Update Submitted That Met QC Criteria: January 24, 2015
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: R727-CL-1001