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This study is designed to assess pharmacokinetics and pharmacodynamics of evolocumab and alirocumab across an appropriate dose range to inform clinical trial operating characteristics for future clinical pharmacology pharmacodynamics similarity studies.
This is a randomized, placebo-controlled, single-dose, parallel arm study in 72 healthy subjects assigned to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (evolocumab and alirocumab ) or placebo.
Full description
This study is designed to assess pharmacokinetics and pharmacodynamics of evolocumab and alirocumab, two monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), across an appropriate dose range to inform clinical trial operating characteristics for future clinical pharmacology pharmacodynamics similarity studies.
This is a randomized, placebo-controlled, single-dose, parallel arm study in 72 healthy subjects assigned to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (evolocumab or alirocumab) or placebo. Evolocumab doses are 21, 35, 70, and 140 mg. Reslizumab doses are 15, 25, 50, and 100 mg . Each arm will include 8 subjects (4 male and 4 female).
Subjects will be admitted for treatment on day -1 and receive a single dose of study drug or placebo on day 1. Depending on the treatment arm, subjects will remain in confinement for one week and continue follow-up through day 42, 56, or 84.
Blood samples (approximately 5 mL per sample) will be collected for determination of plasma concentrations for study drug. Additional blood samples will be collected for lipid analysis and determination of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) (5 mL per sample; pharmacodynamic measure) and exploratory proteomics analyses (5 mL per sample).
Safety evaluations will include adverse event (AE) monitoring, vital sign measurements, and physical examinations. All AEs reported by the subject or observed by the investigator or clinical research unit (CRU) staff will be recorded. Any AE reported after the informed consent is signed and before study drug application will be recorded as medical history.
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Inclusion criteria
Exclusion criteria
Subject is taking cholesterol medication (e.g. statins).
Subject is anemic (i.e., with hematocrit or hemoglobin less than the lower limit of normal) or has any chronic condition(s) that may impact blood sample collection.
Subject has had previous exposure to the biologic evolocumab or alirocumab.
Subject has a history of asthma.
Subject has a history of anaphylaxis from environmental exposures such as peanuts or bee stings.
Subject has an allergic history that includes urticaria, angioedema or respiratory coughing or bronchospasm.
Subject has a history of severe local reactions or generalized erythema from skin allergen testing.
Subject has used any prescription or nonprescription drugs (including aspirin or NSAIDs and excluding oral contraceptives and acetaminophen) within 14 days or 5 half-lives (whichever is longer) or complementary and alternative medicines within 28 days before the first dose of study drug.
Subjects are currently participating in another clinical study of an investigational drug or are have been treated with any investigational drug within 30 days or 5 half-lives (whichever is longer) of the compound.
Subject has used nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff) within 6 weeks of Screening.
Subject has consumed alcohol, xanthine containing products (e.g., tea, coffee, chocolate, cola), caffeine, grapefruit, or grapefruit juice within 48 hours of dosing. Subjects must refrain from ingesting these throughout the study.
Subject has any underlying disease or surgical or medical condition (e.g., cancer, human immunodeficiency virus [HIV], severe hepatic or renal impairment) that could put the subject at risk or would normally prevent participation in a clinical study. This includes subjects with any underlying medical conditions that put subjects at higher risk for coronavirus disease of 2019 (COVID-19) complications; per current Center for Disease Control and Prevention (CDC) recommendations this includes:
Subject has any signs or symptoms that are consistent with COVID-19. Per current CDC recommendations this includes subjects with the symptoms cough or shortness of breath or difficulty breathing, or at least two of the following symptoms: fever, chills, repeated shaking with chills, muscle pain, headache, sore throat or new loss of taste/smell. In addition, the subject has any other findings suggestive of COVID-19 risk in the opinion of the investigator.
Subject tests positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by a molecular diagnostic test performed prior to admission.
Subject has known or suspected allergies or sensitivities to any study drug.
Subject has clinical laboratory test results (hematology, serum chemistry lipid panel and comprehensive metabolic panel) at Screening that are outside the reference ranges provided by the clinical laboratory and considered clinically significant by the investigator.
Subject has a positive test result at Screening for human immunodeficiency virus (HIV) 1 or 2 antibody, hepatitis C virus load, hepatitis C virus antibodies, or hepatitis B surface antigen.
Subject is unable or unwilling to undergo multiple venipunctures for blood sample collection because of poor tolerability or poor venous access.
Female subjects are pregnant or lactating before enrollment in the study
Primary purpose
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Interventional model
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72 participants in 9 patient groups, including a placebo group
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Data sourced from clinicaltrials.gov
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