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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hypercholesterolemia, LDL Cholesterol

Intervention / Treatment
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* Drug: LGT209 50 mg
* Drug: LGT209 300 mg
* Drug: Placebo
* Drug: Statins (atorvastatin or simvastatin)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacodynamics, Hypercholesterolemia,, LDL cholesterol lowering,, proprotein convertase subtilisin/kexin type 9 (PCSK9),, LGT209,, drug safety,, pharmacokinetics,