Title
Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Liposomal siRNA in Subjects With High Cholesterol
A Placebo-Controlled, Single-Blind, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PRO-040201 in Male and Female Subjects With Hypercholesterolemia
Phase
Phase 1Lead Sponsor
Arbutus Biopharma CorporationStudy Type
InterventionalStatus
TerminatedIndication/Condition
HypercholesterolemiaIntervention/Treatment
pro-040201 ...Study Participants
23This study is a Phase 1, single-center, placebo-controlled, single-blind, first-in-human, single-ascending dose study in male and female subjects with high cholesterol. A maximum of 32 subjects is planned for enrollment in this study.
Single dose IV infusion
placebo
Inclusion Criteria: Fasting, stable LDL-C ≥ 160 mg/dL Fasting, stable triglyceride < 400 mg/dL BMI between 22 and 35 kg/m2, inclusive Females must be of non-child bearing potential Males of reproductive potential must agree to practice effective contraception throughout the study and for 3 months following infusion Exclusion Criteria: Clinically significant endocrine, hematologic, renal, hepatic, pulmonary, uncontrolled psychiatric, or neurologic disease Cancer within 5 years prior to screening History of congestive heart failure or chronic heart failure Uncontrolled cardiac arrhythmias History of coronary heart disease Clinically significant abnormal baseline ECG History of additional risk factors for torsades de pointes Hepatitis B, C, or HIV positive Current diagnosis or known history of liver disease A marked baseline prolongation of QT/QTc interval Known history of fibromyalgia, myopathy, myositis, rhabdomyolysis, any unexplained muscle pain, or a creatine phosphokinase (CPK) >3 x upper limit of normal (ULN) at screening Alanine aminotransferase, AST, GGT, or total bilirubin >2 x ULN at screening Serum creatinine > 1.5 mg/dL Systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg on 2 occasions during screening Concomitant use of medications that prolongs the QT/QTc interval Treatment with lipid lowering therapy within 30 days prior to screening Use of investigational drug within 3 months prior to screening
