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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE March 30, 2010
First Posted Date  ICMJE April 1, 2010
Last Update Posted Date June 21, 2017
Study Start Date  ICMJE February 2010
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 31, 2010)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 11, 2012)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: March 31, 2010)
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Concentration-Controlled Ribavirin for the Treatment of Patients With Chronic Hepatitis C Virus Infection
Official Title  ICMJE Concentration-Controlled Ribavirin for the Treatment of Patients With Chronic Hepatitis C Virus Infection
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis C Virus
Intervention  ICMJE Drug: ribavirin
Randomization to standard weight based ribavirin dosing (1000 or 1200 mg daily) or concentration-guided dosing based on first dose AUC0-12
Study Arms  ICMJE
  • 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
Publications * 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.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 6, 2015)
15
Original Estimated Enrollment  ICMJE
 (submitted: March 31, 2010)
40
Actual Study Completion Date  ICMJE August 2015
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01097395
Other Study ID Numbers  ICMJE 08-1198
K23DK082621 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Colorado, Denver
Study Sponsor  ICMJE University of Colorado, Denver
Collaborators  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE
Principal Investigator: Jennifer J Kiser, PharmD University of Colorado, Denver
PRS Account University of Colorado, Denver
Verification Date June 2017

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