TMC435-TiDP16-C126 - Trial to Investigate the Effect of Severe Renal Impairment on the Pharmacokinetics and Safety of TMC435
Condition: Hepatitis C Virus
MeSH terms: Hepatitis C; Hepatitis
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to assess the steady-state pharmacokinetics of TMC435 in
      participants with severe renal impairment and to compare these with the TMC435
      pharmacokinetics in matched participants with normal renal function. We will also study the
      short-term safety and tolerability of TMC435, when administered in participants with severe
      renal impairment and in participants with normal renal function. 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. TMC435 is being investigated for the treatment of chronic
      hepatitis C virus (HCV) infection. 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). The result of this study may provide dosing recommendations for TMC435 in
      patients with severe renal impairement. This is a Phase I, open-label (both participant and
      investigator know the name of the medication given at certain moment), to investigate the
      effect of severe renal impairment on the pharmacokinetics and safety of TMC435. Severe renal
      impairment will be defined by an estimated glomerular filtration rate (eGFR) = 29
      mL/min/1.73m2. Participants with severe renal impairment are only allowed in this study if
      they are not on dialysis. Normal renal function will be considered as an eGFR = 80
      mL/min/1.73m2. eGFR is a measured filtering capacity of the kidneys. The trial population
      will consist of a total of 16 male or female participants. Eight (8) healthy participants
      with a normal renal function and 8 participants with severe renal impairment will be
      included. A healthy participant will be matched to a participant with severe renal impairment
      with regards to sex, race, age (± 10 years), and body mass index (BMI) (± 20%). Dosing of the
      matched healthy participants can only start once the corresponding participants with severe
      renal impairment has completed Day 10 assessments (including physical examination). All
      participants will receive TMC435150 mg once a day (q.d.) for 7 days under fed conditions.
      Blood and urine samples, electrocardiogram (ECG) and vital signs (blood pressure and heart
      rate) will be taken at screening, on Day 1, Day 7, at the follow-up visit at 1 week after
      last dose of study medication and at the follow-up visit at 4-5 weeks after last dose of
      study medication. A physical examination will be performed at screening, on Day -1 (= day
      before first medication intake), on Day 10 and during the follow-up visits. A full
      pharmacokinetic profiles of bound TMC435 will be determined on Day 7 up to 72 hours postdose.
      In addition, unbound TMC435 plasma concentrations will be determined at specified timepoints.
      Safety and tolerability will be monitored throughout the trial. Participants will be admitted
      to the unit on Day-1 and discharged on Day10. Each participant will receive orally 150 mg
      TMC435, q.d. for 7 consecutive days.
    

Intervention name(s): TMC435
Intervention type(s): Drug
Intervention description(s): 150 mg capsule once daily for 7 days
Intervention MeSH terms: Simeprevir
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: TMC435-TiDP16-C126; TMC435-C126; TMC435; HCV; Hepatitis C; Hep C; severe renal impairement