TMC647055HPC1001 - First-in-human Trial to Examine Safety, Tolerability and Pharmacokinetics (How the Drug is Absorbed Into the Bloodstream) of Increasing Single Oral Doses and of Increasing Repeated Oral Doses of TMC647055 in Healthy Volunteers and in Hepatitis C Virus Infected Patients
Condition: Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to assess the safety and tolerability of TMC647055 both after
      increasing single oral doses from 100 mg up to maximum 3000 mg in fed conditions, and after
      multiple oral doses in fed conditions at increasing dose levels administered for 6 days, as
      well as to assess the pharmacokinetics of TMC647055 after increasing single oral doses from
      100 mg up to maximum 3000 mg in fed conditions, and after multiple oral doses in fed
      conditions at increasing dose levels administered for 6 days and to assess the effect of food
      on a single oral dose of TMC647055 at one dose level, all in healthy participants. In
      addition, the safety, tolerability, pharmacokinetics and the antiviral activity of TMC647055
      will be determined after 6 days of consecutive dosing and of TMC647055 and TMC435 after 10
      days of co-administration in chronic hepatitis C virus infected patients. Pharmacokinetics
      means how the drug is absorbed into the bloodstream, distributed in the body and eliminated
      from the body. TMC647055 is being investigated for the treatment of chronic hepatitis C
      infection.
    

Detailed description: 
      TMC647055 is being investigated for the treatment of chronic hepatitis C infection. This is a
      first-in-human, double-blind (sponsor, investigator and participant do not know which
      treatment is given), randomized (like flipping a coin), placebo-controlled, single centre,
      Phase I study in healthy volunteers to examine the safety, tolerability, and plasma
      pharmacokinetics of increasing single oral doses and of increasing repeated oral doses of
      TMC647055, followed by a double-blind repeated-dose part in chronic hepatitis C virus (HCV)
      infected patients. The study population will consist of 45 healthy adult volunteers between
      18 and 55 years of age and 10 or 20 chronic HCV-genotype 1 infected patients between 18 and
      65 years of age. The single dose escalation part of the trial will include 2 panels (Panels 1
      and 2) of 9 participants each. There will be 6 sessions (Sessions I to VI): panel 1 will do
      sessions I, III & V; panel 2 will do sessions II, IV and VI. In each session, 6 participants
      will receive TMC647055 and 3 participants will receive placebo with standard meals. Over 3
      sessions, each participant will receive TMC647055 twice and placebo once. The dose of
      TMC647055 will be consecutively increased. Planned doses will be 100 mg, 250 mg, 600 mg, 1250
      mg, 2000 mg, and 3000 mg of TMC647055 or placebo, administered as a single oral
      administration. A wash out period of at least 10 days will be respected between 2 sessions of
      1 panel. Doses may be adapted pending the safety and pharmacokinetic outcome of the previous
      sessions but will not exceed the limit of 3000 mg. Dose increase will only occur if the
      previous dose is shown to be generally safe and tolerable. For precautionary safety reasons,
      the dose administration in sessions IV, V and VI will be staggered: the first 4 to 5
      participants of the panel will receive the dose at least 24 hours prior to the second group
      of 4 to 5 participants. To investigate the effect of food, one single dose will be tested in
      fasted conditions (Session VII). The dose of TMC647055 tested in this session will be derived
      from the results obtained in Sessions I to V. Participants who received TMC647055 at the
      selected dose with standard meals in Sessions I to V will again receive TMC647055 in fasted
      conditions in Session VII. Participants who received placebo will receive placebo again. The
      multiple-dose escalation part of the trial (sessions VIII, IX and X) will include 3 panels
      (Panels 3, 4, and 5) of 9 participants each: panel 3 will do session VIII, panel 4 session IX
      and panel 5 session X. In all panels, TMC647055 or placebo will be administered during 6
      consecutive days, with on Day 6 a morning dose only. Medication is anticipated to be given
      either every 8 hours, every 12 hours or every 24 hours. This can be changed per dosing
      session following the outcome of the previous session. In each multiple dosing session, 6
      participants will receive TMC647055 and 3 participants will receive placebo. The multiple
      dose escalation part will be started when the doses of Sessions I, II, III, and IV are found
      to be generally safe and tolerable based upon review of the blinded safety and
      pharmacokinetic data. Dose increase will only occur if the previous dose is shown to be
      generally safe and tolerable. The initial daily dose tested in Panel 3 will not be higher
      than the doses tested in Sessions I to IV. After the healthy volunteer sessions, there will
      be 3 sessions in chronic HCV infected patients (sessions XI, XII and XIII). Session XI will
      be started when the doses in healthy volunteers are found to be generally safe and tolerable
      and a selected dose will be given every 12 hours. The total daily dose will not exceed the
      highest daily dose and exposure shown to be generally safe in the multiple dose escalation in
      healthy volunteers. The dose for session XII will be selected based on the results from
      session XI and will be given every 12 hours or every 8 hours. In each session, 8 patients
      will receive TMC647055 and 2 patients will receive placebo. TMC647055 will be given during 6
      consecutive days with on day 6 a morning dose only. Session XIII will be open-label and will
      consist of 2 treatment arms. In treatment arm 1, 8 patients will receive TMC647055 (1000 mg
      twice a day) co-administered with TMC435 (150 mg once daily) for 10 days.In treatment arm 2,
      8 subjects will receive TMC435 (150 mg once daily) for 6 days. Safety and tolerability will
      be evaluated continuously by checking illnesses and side effects, by taking blood and urine
      samples, by electrocardiograms and telemetry (electrical recording of the heart, only for
      healthy volunteers), by taking blood pressure and heart rate and by performing physical
      examinations. TMC647055 or placebo will be given as an oral solution, ranging from 100 to
      3000 mg in the single dose part, in the multiple dose part during 6 consecutive days either
      every 8 hours, 12 hours or 24 hour. In sessions XI and XII, TMC647055 or placebo will be
      given every 8 or 12 hours at dose and frequency determined by results of the previous
      sessions. In session XIII, the dose of TMC647055 will be 1000 mg twice a day and TMC435 will
      be given as oral capsules at 150 mg once daily.
    

Intervention name(s): TMC647055; Placebo; TMC647055; TMC647055; Placebo; TMC435; Placebo; TMC647055; Placebo; TMC647055
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): One single dose as oral solution, doses from 100 mg up to a maximum of 3000 mg increasing in sessions I through VI.; Oral solution given in session XI every 12 hours, in session XII every 12 or 8 hours. Doses and regimen will be determined based on outcome of previous sessions.; Oral solution given in session XIII, treatment arm 1 during 10 days at a dose of 1000 mg every 12 hours.; In sessions VIII through X, oral solution given once daily, every 12 hours or every 8 hours on 6 consecutive days. Doses are based on outcome of previous sessions.; One single dose as oral solution, selected dose ranging between 100 and 3000 mg in session VII; Oral capsule given in session XIII, in treatment arm 1 during 10 days and in treatment arm 2 during 6 days at a dose of 150 mg once daily.; One single dose as oral solution, selected dose ranging between 100 and 3000 mg in session VII; One single dose as oral solution, selected dose ranging between 100 and 3000 mg in session VII; In sessions VIII through X, oral solution given once daily, every 12 hours or every 8 hours on 6 consecutive days. Doses are based on outcome of previous sessions.; Oral solution given in session XI every 12 hours, in session XII every 12 or 8 hours. Doses and regimen will be determined based on outcome of previous sessions.
Intervention MeSH terms: Simeprevir
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: HCV genotype 1 infected patients; TMC647055HPC1001; TMC647055; HPC; Hepatitis C; Healthy volunteers; TMC435