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

This study has been terminated.
(Potential for immune stimulation to interfere with further dose escalation.)
Sponsor:
Information provided by:
Tekmira Pharmaceuticals Corporation
ClinicalTrials.gov Identifier:
NCT00927459
First received: June 23, 2009
Last updated: January 21, 2010
Last verified: January 2010
  Purpose

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.


Condition Intervention Phase
Hypercholesterolemia
Drug: PRO-040201
Drug: Placebo
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Tekmira Pharmaceuticals Corporation:

Primary Outcome Measures:
  • Safety and tolerability of PRO-040201 [ Time Frame: 29 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics of PRO-040201 in Humans [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Pharmacodynamics of PRO-040201 in Humans [ Time Frame: 29 days ] [ Designated as safety issue: No ]

Enrollment: 23
Study Start Date: June 2009
Study Completion Date: January 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PRO-040201
PRO-040201 with placebo control in each cohort
Drug: PRO-040201
Single dose IV infusion
Placebo Comparator: Placebo
PRO-040201 with placebo control in each cohort
Drug: Placebo
placebo

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00927459

Locations
United States, Ohio
Medpace Clinical Pharmacology Unit
Cincinnati, Ohio, United States, 45212
Sponsors and Collaborators
Tekmira Pharmaceuticals Corporation
Investigators
Principal Investigator: Douglas Logan, MD Medpace Clinical Pharmacology Unit
  More Information

No publications provided

Responsible Party: Mark Murray, PhD, CEO, Tekmira Pharmaceuticals Corporation
ClinicalTrials.gov Identifier: NCT00927459     History of Changes
Other Study ID Numbers: TKM-ApoB-001
Study First Received: June 23, 2009
Last Updated: January 21, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Tekmira Pharmaceuticals Corporation:
cholesterol
coronary artery disease

Additional relevant MeSH terms:
Hypercholesterolemia
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on October 23, 2014