Pharmacodynamic Biomarkers to Support Biosimilar Development: PCSK9 Inhibitors

Inclusion Criteria

• Subject signs an institutional review board (IRB)-approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization) before any study related procedures are performed.
• Subject is a healthy man or woman, 18 to 55 years of age, inclusive, who has a body mass index of 18.5 to 32 kg/m2, inclusive, at Screening.
• Subject has a LDL-C level >=100 and <=190 mg/dL inclusive, at Screening.
• Subject has normal medical history findings, clinical laboratory results, vital sign measurements, 12 lead electrocardiogram (ECG) results, and physical examination findings at Screening or, if abnormal, the abnormality is not considered clinically significant (as determined and documented by the investigator or designee).
• Subject must have a negative test result for alcohol and drugs of abuse at screening and Check-in (Day -1).
• Female subjects must be of non-childbearing potential or, if they are of childbearing potential, they must: 1) have been strictly abstinent for 1 month before Check in (Day -1) and agree to remain strictly abstinent for the duration of the study and for at least 1 month after the last application of study drug; OR 2) be practicing 2 highly effective methods of birth control (as determined by the investigator or designee; one of the methods must be a barrier technique) from at least 1 month before Check in (Day -1) until at least 1 month after the last application of study drug.
• Male subjects must agree to practice 1 highly effective method of birth control (as determined by the investigator or designee) from at least 1 month before Check in (Day-1) until at least 1 month after the last application of study drug.
• Subject is highly likely (as determined by the investigator) to comply with the protocol defined procedures as to complete the study.

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:
• People with chronic lung disease or