Study in Healthy Volunteers of the Safety and Metabolism of Different Doses of the Anti-HIV Drug TMC278LA.
Condition: HIV Infection
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      TMC278 (also called rilpivirine) is a new drug being developed to treat HIV. Usually TMC278
      is taken as a tablet, by mouth, once a day, but a 'long acting' formulation has been
      developed so the drug stays in the bloodstream for a longer time - this allows the drug to be
      given by injection and less often. It is hoped that this injectable version of the drug may
      be used to help prevent HIV transmission in the future by giving it to people who are at risk
      of HIV. This is similar to the way travellers to areas with malaria may take antibiotics to
      prevent infection. The investigators aim to investigate the feasibility of using TMC278 as a
      preventative medication by performing this study.

      The purpose of this study is to investigate the levels of drug which can be measured in the
      blood, as well as the tissues and fluids of the rectum (the lowest part of the bowels just
      before the opening of the anus) as well as the safety of the drug and how well tolerated it
      is when given as a single dose. In this study, the investigators will not be investigating
      whether the drug prevents HIV so the investigators will recruit people who are HIV negative,
      and whose lifestyle does not put them at risk of becoming infected before or during the
      study.

      If the study shows the drug is well tolerated and produces appropriate levels of the drug (in
      the bloodstream and the rectal compartment) to suggest that it could be effective, it will
      help design future studies looking at preventing HIV.
    

Detailed description: 
      The trial will examine the pharmacokinetics of doses of 300mg and 600mg, as well as either
      150mg or 1200mg, of TMC278LA, given as a single intramuscular dose to HIV-negative
      participants. Investigation of drug pharmacokinetics in plasma, female genital secretions and
      tissue samples, and male rectal fluid and tissue samples (at the 600mg dose) will be also
      carried out in order to provide data on relative drug exposure following drug administration.
      Additionally, ex-vivo assays to assess viral inhibition in fluid from genital secretions and
      rectal compartments will provide partial information on pharmacodynamic characteristics of
      TMC278; this may usefully inform future selection decisions on the appropriate target
      concentrations required for prevention.

      The target concentration for a prophylactic use of TMC278 in plasma, genital or rectal
      tissues and fluids is unknown. It is possible that a target lower than that required for
      treatment of established infection would be suitable. However, there is currently no
      pharmacodynamic data to usefully inform what this target concentration might be. In the
      absence of population PK data in an efficacy trial of TMC278 as a prophylactic agent, the
      investigators aim to obtain useful indirect data from ex-vivo viral inhibition assays to at
      least guide future decisions on dose selection.

      Up to 60 evaluable female participants will be enrolled, with more than 40% being of African
      ancestry. Six male participants will also be enrolled. This will provide data on plasma
      pharmacokinetics and the relative distribution kinetics in the female genital tract and male
      rectal compartment in order to support expanded safety studies and a phase III global
      efficacy trial.
    

Intervention name(s): 300mg TMC278LA; 150mg TMC278LA; 1200mg TMC278LA; 600mg TMC278LA
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 300mg TMC278LA intramuscular injection; 150mg TMC278LA intramuscular injection; 1200mg TMC278LA intramuscular injection; 600mg TMC278LA intramuscular injection
Other intervention name(s): rilpivirine long-acting; rilpivirine long-acting; rilpivirine long-acting; rilpivirine long-acting
Intervention MeSH terms: Rilpivirine
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: HIV