Drug Interaction Study With Ribavirin and Abacavir in Male Subjects With Hepatitis C Who Have Failed Ribavirin Treatment
Condition: Hepatitis C; HIV
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Intervention: Ribavirin; Ribavirin plus Abacavir (ABC)
Intervention description: Daily Ribavirin alone 400 mg in the morning (AM) and 600 mg in the afternoon (PM) orally with 12 hours between the doses (Body Weight ≤75 kg)
OR
Daily RBV alone 600 mg orally every 12 hours (Body Weight >75 kg); Daily Ribavirin 400 mg in AM and 600 mg in PM orally with 12 hours between the doses (Body Weight ≤75 kg)
OR
Daily RBV 600 mg orally every 12 hours (Body Weight >75 kg)
Plus
Daily Abacavir 300 mg orally every 12 hours
Intervention MeSH terms: Ribavirin; Abacavir
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      This research is being done to find out whether abacavir (Ziagen®) lowers the levels of
      ribavirin (Ribapak®) in the body of persons taking these two drugs.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Hepatitis C Virus (HCV) -monoinfected subjects who either successfully completed
             (defined as cured) or previously failed RBV-based therapy for hepatitis C infection,
             and are currently not receiving therapy for hepatitis C; at least 18-64 years of age.
             HCV cure is defined as a sustained undetectable viral response at 24 weeks post
             treatment.

          -  Females who are not of reproductive potential (defined as women who have been
             postmenopausal for at least 24 consecutive months or who have undergone hysterectomy,
             bilateral oophorectomy, or bilateral tubal ligation.

          -  Negative serum β- human chorionic gonadotropin (HCG)

          -  Negative HIV-1 serology documented by any licensed Enzyme-linked immunoassay (ELISA)
             test kit within 30 days prior to study entry.

          -  Positive HCV antibody documented within 30 days prior to study entry.

          -  Negative Human Leukocyte Antigen (HLA)-B*5701 test documented within 30 days prior to
             study entry.

          -  Ability and willingness of subject to provide a signed informed consent and comply
             with study requirements.

          -  All subjects must not participate in a conception process (e.g., active attempt to
             impregnate, sperm donation, in vitro fertilization). If participating in sexual
             activity that could lead to pregnancy, male subjects must take every precaution to
             avoid risk of pregnancy for their female partners by using reliable contraception
             (condom) while receiving study therapy and for 6 months following permanent
             discontinuation of study therapy. Subjects will also be instructed to counsel their
             female partners regarding fetal risk and need for appropriate contraception (e.g.,
             hormonal, barrier) so as a secondary effort to prevent pregnancy even though the
             female partners will not be study participants.

          -  Estimated creatinine clearance ≥50 mL/minute, within 30 days prior to study entry

          -  Laboratory values obtained within 30 days prior to study entry:

          -  Hgb within the normal limits as defined by the reporting laboratory

          -  Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and alkaline
             phosphatase >5 x upper limit of normal (ULN) as defined by the reporting laboratory.

          -  Direct bilirubin ≤1.5 x ULN as defined by the reporting laboratory.

          -  Follicle Stimulate Hormone (FSH) measurement elevated into the menopausal range for
             females who report being postmenopausal for at least 24 consecutive months is required
             at screening for all female subjects.

          -  Subject has not consumed alcohol in the 48 hours prior to the administration of study
             drugs.

          -  Framingham cardiovascular disease risk score <10%.

        Exclusion Criteria:

          -  As determined by the investigator, a significant active or previous history of
             cardiovascular, renal, hematologic, neurologic, gastrointestinal, psychiatric,
             endocrine, or immunologic disease (s). This inclusive of chronic illnesses such as
             hypertension, coronary artery disease, arthritis, diabetes, any chronic
             gastrointestinal condition that may affect drug absorption. History of chronic or
             acute medical condition that in the opinion of the investigator would jeopardize
             safety of subjects participating in this study. Any other medical or psychological
             condition that might, in the opinion of the site investigator, interfere with
             participation in the study or put subjects at undue risk.

          -  History of anemia, hemoglobinopathy or any other cause of or tendency to hemolysis.

          -  History of RBV-induced anemia that required dose reduction or discontinuation of RBV
             therapy while receiving treatment for hepatitis C infection in the past. Patients who
             required treatment with erythropoietin or blood transfusion for the management of
             RBV-associated anemia will be excluded from participating in the study.

          -  Use of prescription or over-the-counter medications, including herbal products, within
             30 days prior to study entry that in the opinion of the investigator would preclude
             study participation.

          -  Pregnant women or men with a pregnant female partner.

          -  Breast feeding

          -  Active drug use or dependence that, in the opinion of the investigator, would
             interfere with adherence to study requirements, and/or currently receiving methadone
             replacement therapy for the treatment of substance abuse.

          -  Inability of abstaining from alcohol-containing beverages for the duration of the
             study.

          -  Hospitalization or therapy for serious illness within 30 days prior to study entry as
             judged by the investigator.

          -  Known or suspected hypersensitivity reaction to study drugs or their formulations.

          -  Participation in any investigational drug study within 30 days prior to study entry.

          -  Active or history of gout disease.