Study in Healthy Volunteers of the Safety and Metabolism of Different Doses of the Anti-HIV Drug TMC278LA.
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||A Pharmacokinetic Evaluation of the Exposure and Distribution of TMC278LA for Use as Pre-exposure Prophylaxis, in Plasma and Genital Tract / Rectal Compartments, Following a Single Intramuscular Dose at Different Doses in HIV-negative Healthy Volunteers.|
- Plasma pharmacokinetics [ Time Frame: 84 days ] [ Designated as safety issue: No ]The plasma pharmacokinetics of TMC278LA at different dose levels up to 84 days after a single intramuscular administration
- TMC278LA concentrations in the genital tract and rectal compartments. [ Time Frame: 84 days ] [ Designated as safety issue: No ]TMC278LA concentrations in the genital tract and rectal compartments following the administration of different doses in HIV-negative healthy volunteers.
- Safety and tolerability of TMC278LA [ Time Frame: 84 days ] [ Designated as safety issue: No ]The safety and tolerability of up to four different doses of TMC278LA administered as a single dose intramuscularly assessed by clinical and laboratory tests and adverse event reporting
- HIV replication in vitro [ Time Frame: 84 days ] [ Designated as safety issue: No ]The effect of the genital and rectal fluid drug concentrations on HIV replication in vitro (pharmacodynamic [PD] analysis)
|Study Start Date:||January 2011|
|Study Completion Date:||June 2012|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
|Experimental: 300mg TMC278LA||
300mg TMC278LA intramuscular injection
|Experimental: 1200mg TMC278LA||
1200mg TMC278LA intramuscular injection
|Experimental: 600mg TMC278LA||
600mg TMC278LA intramuscular injection
|Experimental: 150mg TMC278LA||
150mg TMC278LA intramuscular injection
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.