Pharmacokinetic Study of a Single Dose of AVI-4065 in Cerebral Spinal Fluid

Encephalitis Clinical Trial

Official title:

Pharmacokinetic Study of AVI-4065 in Cerebral Spinal Fluid Among Healthy Adult Males Following Subcutaneous Administration

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00381433
• Other study ID #: AVI-4065-21c
• Status: Completed
• Phase: Phase 1
• First received: September 25, 2006
• Last updated: July 6, 2009
• Start date: September 2006
• Est. completion date: June 2009

Study information

• Verified date: July 2009
• Source: Sarepta Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

AVI-4020 Injection, a phosphorodiamidate Morpholino oligomer (PMO), was found to cross the blood-brain barrier during a study of patients with presumptive West Nile virus disease. AVI-4065, which was designed to target HCV, is also a PMO; its ability to cross the blood-brain barrier is unknown. In this study, a single dose of AVI-4065 will be subcutaneously injected, and samples collected to determine if this drug crosses the blood-brain barrier. If it does, then additional investigations could be performed in people with severe forms of HCV disease in which the brain is affected.

Description:

AVI-4020 Injection, a phosphorodiamidate Morpholino oligomer (PMO), was found to cross the blood-brain barrier during a study of patients with presumptive West Nile virus disease. AVI-4065, which was designed to target HCV, is also a PMO; its ability to cross the blood-brain barrier is unknown. As the incidence of HCV disease has grown, the knowledge base of this disease has likewise increased.

Encephalopathy is a recognized consequence in some patients with HCV infection. In this study, a single dose of AVI-4065 will be subcutaneously injected, and samples collected to determine if this drug crosses the blood-brain barrier. If it does, then additional investigations could be performed in people with HCV disease in which the brain is affected.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: June 2009
• Est. primary completion date: October 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• Adult males 18 years to 64 years of age;

• Good general health (as evidenced by no chronic conditions, normal physical exam, vital signs within normal limits; laboratory evaluations within normal range)

• Signed and dated written informed consent form; and

• Willing to participate in all study activities and all requirements, including effective contraception (viz., a double-barrier method) during the 7-day study surveillance period.

Exclusion Criteria:

• Hematology, serum chemistry (exclusive of electrolytes), and urinalysis laboratory test values >2 times upper limits of normal or anemia (hemoglobulin <11 g/dL), leukopenia (total white blood count <3,000/µL or total neutrophils <1,500/ µL) or thrombocytopenia (platelets <100,000/µL). Electrolytes and coagulation values exceeding normal ranges are to be excluded.

• Body Mass Index (BMI) >35.

• Calculated creatinine clearance (by the Cockroft and Gault Formula) <70 mL/min, based on age and gender.

• Positive HIV-1 or HIV-2 serology.

• Positive HCV serology and/or positive plasma HCV-RNA status.

• Positive HBsAg or HBcAb status.

• Solid or hematopoetic organ transplant recipient.

• Active illness or recent illness within 30 days of the first dose of study drug.

• History of any of the following: brain injury, neoplasm, chronic or migraine headaches, cancer, meningitis or hydrocephalus.

• Usage of any prescribed, over-the-counter or illicit drug(s) within 30 days of study drug administration. Use of herbal remedies and/or supplements at the discretion of the Investigator.

• Unwilling to practice effective contraception during the study period.

• Participation in any clinical interventional trial within the previous 6 months.

• Positive drug urine screen.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Encephalitis

Intervention

Drug:
• AVI-4065 Injection

Locations

Country	Name	City	State
United States	NW Kinetics	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Sarepta Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine if the study drug penetrates the blood brain barrier following a single intravenous dose, and if so, the associated CSF, plasma and urine pharmacokinetics.
Secondary	Safety
Secondary	Tolerability