A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of IONIS FXI-LRx in up to 84 Healthy Volunteers

Inclusion Criteria * Body mass index (BMI) ≤ 35 kg/m2 * Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal * Males must be surgically sterile, abstinent or, if engaged in sexual relations with a female of child-bearing potential, the subject must be using an acceptable contraceptive method from the time of signing the informed consent form until at least 30 days (single-dose cohorts) or 13 weeks (multiple-dose cohorts) after the last dose of Study Drug * Willing to refrain from strenuous exercise/activity for at least 72 hrs prior to study visits * Must abstain from alcoholic beverages for at least 48 hrs prior to clinic visits and not increase alcohol consumption during the study Exclusion Criteria * Clinically-significant abnormalities in medical history, screening laboratory results, physical examination that would render a subject unsuitable for inclusion. Including but not limited to: * Platelet count \< LLN * INR \> 1.4 * aPTT \> ULN * FXI activity \< 0.7 U/mL * Treatment with another investigational drug, biological agent, or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer * Any history of previous treatment with an oligonucleotide * History of bleeding diathesis or coagulopathy * Uncontrolled hypertension (BP \> 160/100 mm Hg)