A Study of Pharmacokinetics, Efficacy, Safety, Tolerability, of the Combination of Simeprevir (TMC435), Daclatasvir (BMS-790052), and Ribavirin (RBV) in Patients With Recurrent Chronic Hepatitis C Genotype 1b Infection After Orthotopic Liver Transplantation
Condition: Hepatitis C, Chronic
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Simeprevir; Daclatasvir; Ribavirin; Cyclosporine; Tacrolimus
Intervention description: Participants will receive 150 milligram capsule of simeprevir orally (by mouth) once daily with food for 24 weeks. In Part 1, if simeprevir pre-dose plasma concentration is greater than 7,300 nanogram per milliliter (ng/mL), participants will receive simeprevir 150 milligram capsule orally every other day to complete 24 weeks of treatment.; Participants will receive 60 milligram tablet of daclatasvir orally once daily for 24 weeks.; Participants will receive 5 or 6 tablets of 200 milligram of ribavirin orally twice a day with food for 24 weeks.; Participants will receive cyclosporine as one of the stable immunosuppressant therapy (no change in dose in the last month) for more than 3 months prior to the screening visit. Cyclosporine will be administered as per the manufacturer's prescribing information for 24 weeks.; Participants will receive tacrolimus as one of the stable immunosuppressant therapy (no change in dose in the last month) for more than 3 months prior to the screening visit. Tacrolimus will be administered as per the manufacturer's prescribing information for 24 weeks.
Intervention MeSH terms: Cyclosporine; Ribavirin; Simeprevir; Tacrolimus; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hepatitis C, Chronic; Recurrent Chronic Hepatitis C; Pharmacokinetics; Simeprevir; Daclatasvir; Ribavirin; Orthotopic Liver Transplantation; TMC435; BMS-790052; RBV

Summary:

      The purpose of the study is to evaluate effect of steady-state (when the amount of drug
      administered (in a given time period is equal to the amount of drug eliminated in that same
      period) of simeprevir and daclatasvir on the steady-state pharmacokinetics (what a medication
      does to the body) of cyclosporine (applicable to Part 1 only) and tacrolimus when
      administered as a combinational regimen in post-orthotopic liver transplantation (OLT)
      participants with recurrent hepatitis C virus (HCV) genotype 1b infection and effectiveness
      of a 24-week treatment regimen containing simeprevir, daclatasvir, and ribavirin (RBV) with
      respect to the proportion of HCV genotype 1b infected post-OLT participants achieving
      sustained virologic response 12 weeks after end of treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Liver transplant between 6 months and 10 years prior to the screening visit

          -  Hepatitis C virus (HCV) genotype 1 subtype b infection confirmed at screening

          -  Screening HCV ribonucleic acid level greater than 10,000 IU/mL

          -  HCV treatment-naïve participants must not have received post orthotopic liver
             transplant treatment with any approved or investigational drug for the treatment of
             HCV

          -  Receiving stable immunosuppressant therapy (ie, no change in dose in the last month)
             with cyclosporine (only allowed in Part 1) or tacrolimus for more than 3 months prior
             to the screening visit

        Exclusion Criteria:

          -  Evidence of acute or chronic hepatic decompensation after the liver transplantation
             (including ascites, bleeding varices or hepatic encephalopathy)

          -  Any liver disease of non-HCV etiology, including current evidence of graft rejection
             except the presence of liver steatosis

          -  Any other clinically significant disease that in the opinion of the investigator would
             be exacerbated by the known effects of ribavirin

          -  Coinfection with HCV of another genotype than genotype 1b, HIV type 1 or 2 (positive
             HIV-1 or HIV-2 antibodies test at screening), and hepatitis B virus (hepatitis B
             surface antigen positive)

          -  Multi-organ transplant that included heart, lung, pancreas, or kidney