GSK-189254

GSK189254 is a highly potent histamine 3 (H3) receptor antagonist which has demonstrated efficacy in the reduction of mechanical hyperalgesia and allodynia in the chronic constriction injury pre-clinical model of neuropathic pain (NP). The mechanism of action of GSK 189254 in the pain model is hypothesised to be via enhanced release of monoamines in the central nervous system (CNS). A similar mechanism of action has also been shown for duloxetine. In this phase I study, the safety and efficacy of GSK189254 will be investigated in the electrical hyperalgesia (EH) model in healthy volunteers to build confidence that the preclinical efficacy demonstrated by this compound will translate into patients.
This study will be conducted as a double-blind, double-dummy, placebo-controlled, incomplete block, two period crossover study. Up to 40 healthy male or female volunteers, aged 18-45 years old, will be randomised into the study in order to achieve 32 evaluable subjects. Subjects will undergo two 3-week treatment periods and will be randomised to receive placebo and either GSK189254 (up to 100µg once daily) or duloxetine (up to 60mg daily). There will be a one week washout between treatment periods. The effects of repeated oral dosing of GSK189254 and duloxetine on secondary hyperalgesia in the EH model will be determined. Subject: GSK189254, Neuropathic pain (NP), H3 antagonist, duloxetine, Electrical hyperalgesia, Phase I, Healthy volunteers, Double blind, Safety, tolerability.