A Study in Healthy Participants Investigating the Effect of TMC435 on the Pharmacokinetics of Immunosuppressants Cyclosporine and Tacrolimus
Condition: Hepatitis C Virus
MeSH terms: Hepatitis C; Hepatitis
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to investigate the effect of steady-state concentrations of
      TMC435 (administered once a day) on the single-dose pharmacokinetics of the
      immunosuppressants cyclosporine and tacrolimus in healthy participants. Cyclosporine and
      tacrolimus are immunosuppressants used to prevent transplant rejection and may therefore
      potentially be coadministered with TMC435 in patients infected with hepatitis C virus that
      undergo liver transplantation. We will also explore the short-term safety and tolerability
      following coadministration of TMC435 at steady-state and (1) cyclosporine or (2) tacrolimus
      after single dosing in healthy participants. Steady-state is a term that means that the drug
      has been given long enough so that the plasma concentrations will remain the same with each
      subsequent dose. Pharmacokinetics (PK) means how the drug is absorbed into the bloodstream,
      distributed in the body and eliminated from the body.
    

Detailed description: 
      TMC435 is a protease inhibitor (PI) and is being investigated for treatment of chronic
      hepatitis C virus (HCV) infection, in combination with Peg-IFN (pegylated interferon) and RBV
      (ribavirin). This is a Phase I, open-label (both participant and investigator know the name
      of the medication given at a certain moment) trial in 28 healthy participants to investigate
      the effect of TMC435 at steady-state on the single dose pharmacokinetics of the
      immunosuppressants cyclosporine and tacrolimus. The trial population will consist of a total
      of 28 healthy participants, equally divided over 2 panels. In Panel 1, each participant will
      receive 2 treatments: a single 100-mg dose of cyclosporine on Day 1 and TMC435 150 mg once
      daily for 10 days on Days 1 to 10, coadministered with a single 100-mg dose of cyclosporine
      on Day 7. In Panel 2, each participant will receive 2 treatments: a single 2-mg dose of
      tacrolimus on Day 1 and TMC435 150 mg each day for 12 days on Days 1 to 12, coadministered
      with a single 2-mg dose of tacrolimus on Day 7. Safety and tolerability will be assessed
      during the study period and during follow up. Blood and urine safety samples,
      electrocardiogram (ECG) and vital signs (blood pressure and heart rate) will be taken at
      screening, Day1, Day 2 (only panel 1), Day 7(only panel 2), Day 8 (only panel 2) and at the
      follow-up visit about 5 to 7 days after last TMC435 intake.
    

Intervention name(s): tacrolimus; TMC435; cyclosporine; TMC435
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): a single 2-mg dose of tacrolimus (on Day 1 in treatment C and on Day 7 in treatment D).; TMC435, 150 mg daily for 12 days (Days 1 to 12 in treatment D).; A single 100-mg dose of cyclosporine (on Day 1 of treatment A and on Day 7 of treatment B).; TMC435, 150 mg daily for 10 days (Day 1 - 10 in treatment B).
Intervention MeSH terms: Cyclosporine; Simeprevir; Tacrolimus; Cyclosporins
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hepatitis C Virus; TMC435; TMC435-TiDP16-C120; TMC435-C120; HCV; Hepatitis C; Hep C; Healthy participants