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

Hypercholesterolemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00927459
• Other study ID #: TKM-ApoB-001
• Status: Terminated
• Phase: Phase 1
• First received: June 23, 2009
• Last updated: January 21, 2010
• Start date: June 2009
• Est. completion date: January 2010

Study information

• Verified date: January 2010
• Source: Arbutus Biopharma Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: January 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• PRO-040201
Single dose IV infusion
• Placebo
placebo

Locations

Country	Name	City	State
United States	Medpace Clinical Pharmacology Unit	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Arbutus Biopharma Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of PRO-040201		29 days	Yes
Secondary	Pharmacokinetics of PRO-040201 in Humans		48 hours	No
Secondary	Pharmacodynamics of PRO-040201 in Humans		29 days	No