Safety, Pharmacokinetics and Pharmacodynamics of LGT209 in Healthy Volunteers With Elevated Cholesterol and in Hypercholesterolemic Patients Treated With Statins

A Randomized, Double-blind, Placebo-controlled, Single Dose, Parallel Group Study to Assess the Safety, Tolerability, Bioavailability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous LGT209 in Hypercholesterolemic Patients on Stable Doses of Atorvastatin or Simvastatin and in Healthy Volunteers

This study is designed to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of LGT209 in hypercholesterolemic patients taking common statin medications and in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia; LDL Cholesterol
• Intervention / Treatment: Drug: Placebo; Drug: LGT209 50 mg; Drug: Statins (atorvastatin or simvastatin); Drug: LGT209 300 mg

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Fort Myers, Florida, United States, 33901-8144
      • Novartis Investigative Site
    • Miramar, Florida, United States, 33025
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers: Male and female subjects 18 to 70 years of age, in general good health with fasting LDL-cholesterol >90 mg/dL and fasting serum triglycerides <400 mg/dL
• Patients on statin therapy: Male and female patients 18 to 70 years of age receiving atorvastatin or simvastatin and with fasting LDL-cholesterol >90 mg/dL and fasting serum triglycerides <400 mg/dL

Exclusion Criteria:

Healthy volunteers:

• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
• Women of child-bearing potential unless using highly effective methods of contraception
• Conditions which might impact the safety or biologic activity of the study drug

Statin patients:

• Use of concomitant medications known to impact the safe use or efficacy of atorvastatin and simvastatin based on drug labels
• Women of childbearing potential unless using highly effective methods of contraception during dosing and for at least 100 days after study drug administration
• Conditions which might impact the safety or biologic activity of the study drug

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patient: LGT209 50 mg; 50 mg LGT209 subcutaneous (SC) (1 mL injection x 1 site) in statin patients	Drug: LGT209 50 mg; Active experimental drug; Drug: Statins (atorvastatin or simvastatin); Stable doses of atorvastatin or simvastatin; Other Names: Atorvastatin; Simvastatin
Experimental: Patient: LGT209 300 mg; 300 mg LGT209 subcutaneous (SC) (1 mL injection x 2 sites) in statin patients	Drug: Statins (atorvastatin or simvastatin); Stable doses of atorvastatin or simvastatin; Other Names: Atorvastatin; Simvastatin; Drug: LGT209 300 mg; Active experimental drug
Experimental: Healthy Volunteers: LGT209 300 mg; 300 mg LGT209 or placebo subcutaneous (SC) (1 mL injection x 2 sites) in healthy volunteers	Drug: LGT209 300 mg; Active experimental drug
Placebo Comparator: Patient: Placebo; matching placebo subcutaneous (SC) of LGT209 50 mg or 300 mg in statin patients	Drug: Placebo; Placebo comparator; Drug: Statins (atorvastatin or simvastatin); Stable doses of atorvastatin or simvastatin; Other Names: Atorvastatin; Simvastatin
Placebo Comparator: Healthy volunteers: Placebo; matching placebo subcutaneous (SC) of LGT209 300 mg in healthy volunteers	Drug: Placebo; Placebo comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of subjects (patients and healthy volunteers) with adverse events, serious adverse events and death	12 weeks
Plasma concentrations of LGT209 following subcutaneous administration	12 weeks
Change from baseline in proprotein convertase subtilisin/kexin type 9 (PCSK9) concentration	baseline and 12 weeks
Change from baseline in low density lipoprotein-cholesterol (LDL-C) concentration	baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma concentrations of atorvastatin in patients	2 weeks
Plasma concentrations of simvastatin in patients	2 weeks
Serum concentrations of PCSK9	12 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CLGT209X2105 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: May 9, 2013
• First Submitted That Met QC Criteria: May 17, 2013
• First Posted (Estimate): May 22, 2013

Study Record Updates

• Last Update Posted (Actual): December 17, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: pharmacodynamics; pharmacokinetics,; Hypercholesterolemia,; LDL cholesterol lowering,; proprotein convertase subtilisin/kexin type 9 (PCSK9),; LGT209,; drug safety,
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Simvastatin
• Other Study ID Numbers: CLGT209X2105