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

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ClinicalTrials.gov Identifier: NCT01097395
Recruitment Status : Completed
First Posted : April 1, 2010
Last Update Posted : June 21, 2017
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
University of Colorado, Denver

March 30, 2010
April 1, 2010
June 21, 2017
February 2010
August 2015   (Final data collection date for primary outcome measure)
ribavirin AUC-12 variability [ Time Frame: steady state (~weeks 9-10) ]
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
Same as current
Complete list of historical versions of study NCT01097395 on ClinicalTrials.gov Archive Site
  • safety - absolute hemoglobin declines [ Time Frame: end of treatment (~48 weeks) ]
  • efficacy - early and sustained virologic response [ Time Frame: EVR (12 weeks) and SVR (24 wks after cessation of treatment) ]
    Compare proportions with EVR and SVR in standard weight-based vs. concentration-guided ribavirin dosing groups
  • safety - absolute hemoglobin declines [ Time Frame: end of treatment ]
  • efficacy - early and sustained virologic response [ Time Frame: EVR (12 weeks) and SVR (24 wks after cessation of treatment) ]
    Compare proportions with EVR and SVR in standard weight-based vs. concentration-guided ribavirin dosing groups
Not Provided
Not Provided
 
Concentration-Controlled Ribavirin for the Treatment of Patients With Chronic Hepatitis C Virus Infection
Concentration-Controlled Ribavirin for the Treatment of Patients With Chronic Hepatitis C Virus Infection
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.
Not Provided
Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Hepatitis C Virus
Drug: ribavirin
Randomization to standard weight based ribavirin dosing (1000 or 1200 mg daily) or concentration-guided dosing based on first dose AUC0-12
  • Active Comparator: Standard Weight-Based Ribavirin Dosing
    1000 mg daily in patients weighing <75 kg and 1200 mg daily in patients weighing ≥ 75 kg
    Intervention: Drug: ribavirin
  • Experimental: Concentration-Controlled Ribavirin Dosing
    Dose adjusted based on first dose AUC0-12
    Intervention: Drug: ribavirin
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
15
40
August 2015
August 2015   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 70 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01097395
08-1198
K23DK082621 ( U.S. NIH Grant/Contract )
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Not Provided
University of Colorado, Denver
University of Colorado, Denver
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Jennifer J Kiser, PharmD University of Colorado, Denver
University of Colorado, Denver
June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP