GSK-2256294

Soluble epoxide hydrolase (sEH) is the metabolizing enzyme of epoxyeicosatrienoic acids (EETs), which may play a role in reducing neuroinflammation and regulating cerebral blood flow after subarachnoid hemorrhage (SAH). Hypotheses: Pharmacologic inhibition of the sEH enzyme is safe and will result in increased EETs availability in the blood and cerebrospinal fluid. This study is a double-blind, placebo-controlled, phase 1b randomized trial to evaluate the safety and efficacy of GSK2256294, a novel soluble epoxide hydrolase inhibitor in patients with aneurysmal SAH.

The study evaluates the effect of GSK2256294 exposure at steady state on pulmonary artery systolic pressure (PASP) in healthy volunteers, under hypoxic conditions, after 7 days of dosing. It is single centre, double blind, randomized, placebo-controlled study to be conducted in approximately 30 healthy volunteers. Subjects will be screened no more than 30 days. Subject will be admitted in clinical unit on Day -1. Subject will be dosed for 7 days in unit in morning on all days except for dosing on Days 3 -6. Dosing on Days 3 -6 will occur at home. Subjects will return to the unit on the evening of Day 6 and remain there until Day 8. Subjects will undergo echocardiography under normoxic and hypoxic on Day 1 pre-dose and on Day 7 post-dose. Subject will be followed up for 28- 32 days after discharge. The maximum estimated time that a subject will be enrolled in the study is 62 days from the screening visit to follow up.