Concentration-Controlled Ribavirin for the Treatment of Patients With Chronic Hepatitis C Virus Infection
Condition: Hepatitis C Virus
MeSH terms: Hepatitis A; Virus Diseases; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Intervention: ribavirin
Intervention description: Randomization to standard weight based ribavirin dosing (1000 or 1200 mg daily) or concentration-guided dosing based on first dose AUC0-12
Intervention MeSH terms: Ribavirin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: ribavirin; pharmacokinetics; Hepatitis C virus

Summary:

      The purpose of this study is to determine if concentration-controlled ribavirin dosing can
      achieve a targeted level of plasma exposures and if it appears safe and effective compared
      with standard weight-based ribavirin dosing. Forty, previously treatment-naive participants
      with genotype 1 disease will be randomized to receive concentration-guided or standard
      weight-based ribavirin. Peginterferon alfa 2a,ribavirin, and telaprevir will be provided
      through the study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Chronic HCV-infected men and women

          -  18-70 years

          -  HCV genotype 1

          -  Deemed ready for HCV treatment by hepatology provider and patient

          -  Allowed medications: all those not specifically listed in the exclusion criteria below
             including medications for peginterferon / ribavirin - related adverse effects:
             acetaminophen, ibuprofen, diphenhydramine, selective serotonin reuptake inhibitors,
             darbepoeitin, erythropoietin, GCSF

        Exclusion Criteria:

          -  previous treatment with interferon, peginterferon, investigational HCV drugs,
             boceprevir, or ribavirin;

          -  baseline absolute neutrophil count (ANC) < 1000/mm3,

          -  platelets < 100,000/mm3,

          -  hemoglobin < 12 g/dL for women and < 13 g/dL for men;

          -  HIV positive serostatus;

          -  HBV positive serostatus;

          -  decompensated liver disease (i.e., ascites, history of esophageal variceal bleeding,
             hepatic encephalopathy);

          -  autoimmune hepatitis

          -  hemoglobinopathy (e.g., sickle cell anemia, thalassemia)

          -  Cockcroft and Gault estimated creatinine clearance < 50 mL/min;

          -  alcohol or illicit drug use that in the opinion of the investigator would interfere
             with study participation and/or impact study results

          -  for females, active pregnancy or any intent to become pregnant during study period or
             for up to 6 months after completing treatment

          -  for males, a pregnant female partner or intent to impregnate a female during study
             period or for up to 6 months after completing treatment

          -  for both sexes an unwillingness to use two forms of contraception during the study
             period and for 6 months after completing treatment. While on telaprevir and for 2
             weeks following discontinuation of telaprevir, females must use two non-hormonal forms
             of contraception;

          -  history of significant or unstable cardiac disease including severe coronary artery
             disease (unstable angina, recent myocardial infarction, chest pain with exertion) or
             congestive heart failure;

          -  receipt of an organ transplant;

          -  malignant neoplastic disease;

          -  chronic pulmonary disease that in the opinion of the study hepatologists would
             preclude treatment with peginterferon and ribavirin (e.g., pulmonary function tests
             ≤70% within the previous 2 years);

          -  history of admission to a psychiatric facility within the previous year;

          -  suicide attempt within the previous 3 years;

          -  concomitant medications including: amantadine, mycophenolate mofetil, and
             investigational HCV compounds, alfuzosin, alfentanil, ergot derivatives
             (dihydroergotamine/ergotamine/ergonovine/methylergonovine), meperidine,
             anti-arrhythmics (quinidine, flecainide, propafenone, amiodarone, bepridil),
             astemizole, terfenadine, buspirone, diazepam, estazolam, oral midazolam, triazolam,
             budesonide, domperidone, eletriptan, eplerenone, fluticasone, pimozide, salmeterol,
             calcium channel blockers (diltiazem, felodipine, nifedipine, nisoldipine, verapamil),
             cisapride, cyclosporine, sirolimus, systemic tacrolimus, atorvastatin, lovastatin,
             simvistatin, sildenafil, tadalafil, verdenafil, antibiotics (clarithromycin,
             erythromycin, telithromycin, troleandomycin), carbamazepine, Phenobarbital, phenytoin,
             nefazodone, St. Johns Wort, antifungals (fluconazole, itraconazole, ketoconazole,
             posaconazole, voriconazole), rifampin, rifabutin, aprepitant, cholestyramine,
             fluvoxamine, mifepreistone, modafinil, systemic dexamethasone. With the exception of
             St. Johns Wort, investigators may use their discretion on use of herbal and dietary
             supplements.

          -  Evidence of severe retinopathy or clinically relevant ophthalmologic disorders