Clinical trial NCT01097395: Concentration-Controlled Ribavirin for the Treatment of Patients With Chronic Hepatitis C Virus Infection
Official title: Concentration-Controlled Ribavirin for the Treatment of Patients With Chronic Hepatitis C Virus Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis C Virus
Keywords: ribavirin
pharmacokinetics
Hepatitis C virus
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2010-04-01
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Ribavirin AUC-12 Variability
timeFrame: steady state (~weeks 9-10)
Secondary outcomes:
measure: Safety - Absolute Hemoglobin Declines
timeFrame: from baseline through end of treatment, up to 48 weeks
measure: Sustained Virologic Response (i.e., Cure)
timeFrame: assessed 12 weeks after stopping treatment
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Jennifer J Kiser, PharmD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wu LS, Rower JE, Burton JR Jr, Anderson PL, Hammond KP, Baouchi-Mokrane F, Everson GT, Urban TJ, D'Argenio DZ, Kiser JJ. Population pharmacokinetic modeling of plasma and intracellular ribavirin concentrations in patients with chronic hepatitis C virus infection. Antimicrob Agents Chemother. 2015 Apr;59(4):2179-88. doi: 10.1128/AAC.04618-14. Epub 2015 Feb 2.