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.
Randomization to standard weight based ribavirin dosing (1000 or 1200 mg daily) or concentration-guided dosing based on first dose AUC0-12
Eligibility
Sex: ALLMin age: 18 YearsMax age: 70 Years
Medical Language ↔ Plain English
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
Locations (1)
University of Colorado Denver
Aurora, Colorado, United States
Outcomes
Primary Outcomes
Ribavirin AUC-12 Variability
Demonstrate that concentration-controlled ribavirin dosing can achieve a targeted level of plasma exposure with reduced variability in the steady-state area-under-the-concentration-time curve (AUC0-12) compared with standard weight-based ribavirin dosing
Time frame: steady state (~weeks 9-10)
Secondary Outcomes
Safety - Absolute Hemoglobin Declines
Time frame: from baseline through end of treatment, up to 48 weeks
Sustained Virologic Response (i.e., Cure)
Compare proportions with SVR in standard weight-based vs. concentration-guided ribavirin dosing groups. Number of participants with sustained virologic response is reported.
Time frame: assessed 12 weeks after stopping treatment