Concentration-Controlled Ribavirin for the Treatment of Patients With Chronic Hepatitis C Virus Infection

NCT ID: NCT01097395

Last Updated: 2021-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2015-08-31

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.

Conditions

Hepatitis C Virus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard Weight-Based Ribavirin Dosing

1000 mg daily in patients weighing \<75 kg and 1200 mg daily in patients weighing ≥ 75 kg

Group Type: ACTIVE_COMPARATOR

ribavirin

Intervention Type: DRUG

Randomization to standard weight based ribavirin dosing (1000 or 1200 mg daily) or concentration-guided dosing based on first dose AUC0-12

Concentration-Controlled Ribavirin Dosing

Dose adjusted based on first dose AUC0-12

Group Type: EXPERIMENTAL

ribavirin

Intervention Type: DRUG

Randomization to standard weight based ribavirin dosing (1000 or 1200 mg daily) or concentration-guided dosing based on first dose AUC0-12

Interventions

ribavirin

Randomization to standard weight based ribavirin dosing (1000 or 1200 mg daily) or concentration-guided dosing based on first dose AUC0-12

Intervention Type: DRUG

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jennifer J Kiser, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado Denver

Aurora, Colorado, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 25645847 (View on PubMed)

Other Identifiers

K23DK082621

Identifier Type: NIH

Identifier Source: secondary_id

View Link

08-1198

Identifier Type: -

Identifier Source: org_study_id