Hepatitis C Virus | Concentration-Controlled Ribavirin for the Treatment of Patients With Chronic Hepatitis C Virus Infection
Hepatitis C Virus research study
What is the primary objective of this study?
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.
Who is eligible to participate?
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
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Hepatitis C Virus
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:ribavirinRandomization to standard weight based ribavirin dosing (1000 or 1200 mg daily) or concentration-guided dosing based on first dose AUC0-12
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Standard Weight-Based Ribavirin Dosing1000 mg daily in patients weighing <75 kg and 1200 mg daily in patients weighing ≥ 75 kg
Concentration-Controlled Ribavirin DosingDose adjusted based on first dose AUC0-12
Start Date: February 2010
Completed Date: August 2015
Phase: Phase 4
Primary Outcome: ribavirin AUC-12 variability
Secondary Outcome: safety - absolute hemoglobin declines
Study sponsors, principal investigator, and references
Principal Investigator: Jennifer J Kiser, PharmD
Lead Sponsor: University of Colorado, Denver
Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)