pharmacokinetic study of a single dose of avi-4065 in cerebral spinal fluid

Conditions: Encephalitis

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.

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.

Keywords: hcv hepatitis c virus