Clinical trial NCT00381433: Pharmacokinetic Study of a Single Dose of AVI-4065 in Cerebral Spinal Fluid
Official title: Pharmacokinetic Study of AVI-4065 in Cerebral Spinal Fluid Among Healthy Adult Males Following Subcutaneous Administration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Encephalitis
Keywords: HCV
Hepatitis C virus
Lead sponsor: Sarepta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2006-09-27
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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 outcomes:
measure: Safety
measure: Tolerability
Other outcomes:
Locations:
city: Tacoma
country: United States
facility: NW Kinetics
state: Washington
Study officials:
affiliation: NW Kinetics
name: Paula M Shaw, MD
role: PRINCIPAL_INVESTIGATOR
References: