First time in human study of GSK225694

• Research type

  Research Study

• Full title

  A single-centre, randomised, double-blind, placebo-controlled, escalating dose study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of GSK2256294 in healthy volunteers, and single and repeat doses of GSK2256294 in adult male moderately obese smokers.

• IRAS ID

  97211

• Contact name

  Joseph Cheriyan

• Eudract number

  2010-021246-22

• Research summary

  Epoxyeicosatrienoic acids (EETs) are formed from arachidonic acid (AA) by liver enzymes. EETs are involved in cardioprotection, including dilating blood vessels (arteries), promoting blood vessel growth and anti-inflammatory activities. EETs are metabolised by soluble epoxide hydrolase (sEH). Reduced EETs may contribute to blood vessel wall dysfunction and vascular inflammation as may be observed in smokers and obese individuals. Animal studies have shown inhibition of sEH preserves the positive effects of EETs on blood vessels and therefore may potentially reduce the risk of developing heart disease. The aim of this GlaxoSmithKline sponsored first time in human study is primarily to assess the safety and tolerability of a sEH inhibitor, GSK2256294. We will also assess the pharmacodynamic effect of repeat dosing GSK2256294 on blood vessel wall function by using forearm blood flow studies in otherwise healthy, obese smokers. There will be 4 cohorts; cohorts 1 and 2 will be single dosing and cohorts 3 and 4 will be repeat dosing. Cohort 1 will involve 12 healthy volunteers. We will administer 2mg, 6mg, 18mg of GSK2256294 and a placebo, each separated by approximately a week. Cohort 2 will involve 12 overweight male smokers. In the same way, we will administer 15mg, 40mg, 100mg of GSK2256294 and a placebo. We will review safety and tolerability after each dose. Cohorts 3 and 4 will involve 15 overweight male smokers. We will administer 14 days of GSK2256294 once daily and/or twice daily, compared with placebo. The dose will depend on the results from cohorts 1 and 2. Including screening, washout and follow up time, cohorts 1 and 2 will take approximately 100 days to complete and cohorts 3 and 4 will take roughly 70 days. The study will be conducted in a specialist Phase 1 clinical research unit, with adequate facilities to ensure safety and compliance.

• REC name

  London - Bloomsbury Research Ethics Committee

• REC reference

  12/LO/1832

• Date of REC Opinion

  8 Jan 2013

• REC opinion

  Further Information Favourable Opinion