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

NCT00927459 | Terminated Phase 1 DMC

• 1 other identifier: TKM-ApoB-001
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypercholesterolemia

Keywords

cholesterol; coronary artery disease

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of PRO-040201

  29 days

Secondary Outcomes (2)

• Pharmacokinetics of PRO-040201 in Humans

  48 hours

• Pharmacodynamics of PRO-040201 in Humans

  29 days

Study Arms (2)

PRO-040201

EXPERIMENTAL

PRO-040201 with placebo control in each cohort

Drug: PRO-040201

Placebo

PLACEBO COMPARATOR

PRO-040201 with placebo control in each cohort

Drug: Placebo

Interventions

PRO-040201 DRUG

Single dose IV infusion

PRO-040201

Placebo DRUG

placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Arbutus Biopharma Corporation: lead

Study Sites (1)

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, 45212, United States

Location

MeSH Terms

Conditions

Hypercholesterolemia; Coronary Artery Disease

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Douglas Logan, MD

  Medpace Clinical Pharmacology Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 23, 2009
• First Posted: June 25, 2009
• Study Start: June 1, 2009
• Primary Completion: December 1, 2009
• Study Completion: January 1, 2010
• Last Updated: January 22, 2010

Record last verified: 2010-01

Locations

US (1)