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

This 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.

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