TMC435350-TiDP16-C101 - A Study to Examine the Safety, Tolerability and Pharmacokinetics of Increasing Oral Doses of TMC435350 After Single and Repeated Dosing
Condition: Hepatitis C
MeSH terms: Hepatitis C
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to examine the safety, tolerability and pharmacokinetics of
      increasing oral doses of TMC435350 after single and repeated dosing, followed by an open
      label repeated dosing session in 6 HCV genotype1 infected patients.
    

Detailed description: 
      This trial is a randomized, double blind, placebo-controlled trial to determine the safety,
      tolerability and pharmacokinetics of TMC435350 after single and multiple oral doses taken by
      healthy non-Hepatitis C Virus infected (non-HCV) participants, followed by an open label
      repeated doses taken by 6 HCV-genotype 1 infected participants (non-placebo controlled). The
      single dose escalation part of the trial will consist of 6 sessions (Sessions Ia to VIa) and
      will include 2 panels of 9 healthy non-HCV infected participants each (Panels 1 and 2). The
      dose of the test drug will be consecutively escalated. Doses of 50 mg, 100 mg, 200 mg, 400
      mg, 800 mg and 1200 mg of TMC435350 or placebo will be administered as a single oral
      administration alternating over the 2 panels. In each session, 6 participants will receive
      active treatment and 3 participants will receive placebo after a breakfast. The treatment
      schedule will ensure that over 3 sessions each particpant will receive active treatment twice
      and placebo once. There is a washout period of at least 10 days between consecutive TMC435350
      or placebo dosings within each panel. Participants of Panel 1 will have an additional session
      to investigate food effect: a single dose of TMC435350 will be tested in fasted conditions
      (Session VIIa). Food effect will be investigated for the 200 mg dose in Panel 1, unless the
      the available concentration of the drug in the blood and safety data from previous sessions
      prove unnecessary. Multiple dosing will be started when Sessions Ia (single dose of 50 mg),
      IIa (single dose of 100 mg) and IIIa (single dose of 200 mg) are found to be safe and
      tolerable. The multiple dose escalation part of the trial will consist of 4 consecutive
      sessions (Sessions Ib to IVb) in 4 panels of 9 healthy non-HCV infected participants each
      (Panels 3, 4, 5 and 6). In each session, 6 participants will receive active treatment and 3
      participants will receive placebo. TMC435350 or placebo will be administered during 5
      consecutive days. As a potential food effect is not yet known, administration will be after a
      meal. Treatment is anticipated to be twice daily with doses of 50 mg, 100 mg, 200 mg and 400
      mg. The available concentration of the drug in the blood will be determined up to 72 hours
      after the first dose, in case a single dose of TMC435350 is given (in Sessions Ia to VIIa
      and, if performed, Session VIIIa). In case of multiple dosing (in Sessions Ib to IVb), full
      pharmacokinetic profiles of TMC435350 will be determined for the first dosage interval (e.g.
      up to 24 hours after the first dose for a b.i.d. regimen) and up to 72 hours after the last
      dose. Safety and tolerability will be evaluated continuously and documented (safety report),
      with 24-hours interim PK data after the last dose, before stepping up to the next dose and
      between each session. After completion of the healthy participant sessions, an open label
      session (Ic) in HCV genotype 1 infected participant will be added. The trial population
      (Panel 7) will include 6 male or female, non-responder HCV-genotype 1 infected participants
      with an HCV viral load of at least 50000 IU/mL. These participants will be treated as Panel 7
      with follow-up visits, after the 5 day dosing period. One dose regimen will be selected which
      was shown to be safe in healthy participants and as close as possible to a maximum tolerated
      dose, which will be administered for 5 days. In addition to drug safety and PK parameters,
      viral loads will be determined in plasma.
    

Intervention name(s): TMC435350; Placebo
Intervention type(s): Drug
Intervention MeSH terms: Simeprevir
Keywords: TMC435350-TiDP16-C101; TMC435350-C101; TMC435350; HCV