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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01097395
First received: March 30, 2010
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention
Hepatitis C Virus
Drug: ribavirin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Concentration-Controlled Ribavirin for the Treatment of Patients With Chronic Hepatitis C Virus Infection

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • ribavirin AUC-12 variability [ Time Frame: steady state (~weeks 9-10) ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • safety - absolute hemoglobin declines [ Time Frame: end of treatment (~48 weeks) ] [ Designated as safety issue: Yes ]
  • efficacy - early and sustained virologic response [ Time Frame: EVR (12 weeks) and SVR (24 wks after cessation of treatment) ] [ Designated as safety issue: No ]
    Compare proportions with EVR and SVR in standard weight-based vs. concentration-guided ribavirin dosing groups


Estimated Enrollment: 40
Study Start Date: February 2010
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard Weight-Based Ribavirin Dosing
1000 mg daily in patients weighing <75 kg and 1200 mg daily in patients weighing ≥ 75 kg
Drug: ribavirin
Randomization to standard weight based ribavirin dosing (1000 or 1200 mg daily) or concentration-guided dosing based on first dose AUC0-12
Experimental: Concentration-Controlled Ribavirin Dosing
Dose adjusted based on first dose AUC0-12
Drug: ribavirin
Randomization to standard weight based ribavirin dosing (1000 or 1200 mg daily) or concentration-guided dosing based on first dose AUC0-12

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01097395

Locations
United States, Colorado
University of Colorado Denver
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Jennifer J Kiser, PharmD University of Colorado, Denver
  More Information

No publications provided

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01097395     History of Changes
Other Study ID Numbers: 08-1198, K23DK082621
Study First Received: March 30, 2010
Last Updated: June 6, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Colorado, Denver:
ribavirin
pharmacokinetics
Hepatitis C virus

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Virus Diseases
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 01, 2014