Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Liposomal siRNA in Subjects With High Cholesterol

Phase 1

Terminated

• Conditions: Hypercholesterolemia
• Interventions: Drug: PRO-040201; Drug: Placebo

• Registration Number: NCT00927459
• Lead Sponsor: Arbutus Biopharma Corporation

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-06
• Study First Submitted: 2009-06-23
• Study First Submitted QC: 2009-06-24
• Study First Posted: 2009-06-25
• Primary Completion: 2009-12
• Status Verified: 2010-01
• Study Completion: 2010-01
• Last Update Submitted: 2010-01-21
• Last Update Posted: 2010-01-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 23

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PRO-040201	PRO-040201	PRO-040201 with placebo control in each cohort
Placebo	Placebo	PRO-040201 with placebo control in each cohort

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of PRO-040201	29 days

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics of PRO-040201 in Humans	48 hours
Pharmacodynamics of PRO-040201 in Humans	29 days

Trial Locations

Locations (1)

Medpace Clinical Pharmacology Unit; 🇺🇸 Cincinnati, Ohio, United States