NCT01762774

A 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

Completed Phase 1 Last updated 9 May 2017

What this trial tests

Phase 1 trial testing GSK2256294 in Pulmonary Disease, Chronic Obstructive in 56 participants. Completed in 1 May 2014.

Timeline

16 January 2013

Primary endpoint
1 May 2014

1 May 2014

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	single group
Masking	double
Primary purpose	treatment
Enrollment	56
Start date	16 January 2013
Primary completion	1 May 2014
Estimated completion	1 May 2014
Sites	1 location across United Kingdom

Drugs / interventions tested

• GSK2256294 — full drug profile →
• Placebo

Conditions studied

• Pulmonary Disease, Chronic Obstructive — all drugs for Pulmonary Disease, Chronic Obstructive →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 18 to 55, male only, with Pulmonary Disease, Chronic Obstructive. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This study is the First Time in Human Study for GSK2256294 and will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and repeat oral doses of GSK2256294 administered to healthy male volunteers (Cohort 1) and otherwise healthy adult male moderately obese smokers (Cohorts 2 to 4). Cohorts 1 and 2 will enrol 12 subjects each and each subject will take part in four study periods. All subjects will receive placebo regimen and three dosing regimens of GSK2256294 in a specified sequence (planned doses 2 mg, 6 mg and 18 mg in Cohort 1 and 15 mg, 40 mg and 100 mg in Cohort 2). Each study period will be followed by a Wash-out period of 7 to 14 days in Cohort 1 and up to 4 weeks in Cohort 2. During each study period subjects will be in-house from Day -1 until the 48 hours post dose assessments have been completed. Subjects will return to the unit as out-patients for remaining post-dose assessments. Subjects will then be followed for 7 to 14 days in Cohort 1 and up to 3 to 4 weeks in Cohort 2. Total duration of the study for Cohort 1 will be 98 days and for Cohort 2 it will be up to 144 days. Cohort 3 and 4 will each recruit 15 subjects. For Cohorts 3 and 4, each subject will take part in one treatment period of 18 days (Day-1 to Day 17) with dosing from Day 1 to Day 14. Subjects will then be followed for 7 to 14 days. Total duration of the study for Cohort 3 and Cohort 4 will be 67 days. Dose selection for Cohorts 3 and 4 will be based on the safety, PK profile and enzyme inhibition obtained in Cohorts 1 and 2. This study will also evaluate the evidence for a functional effect of soluble Epoxide Hydrolase (sEH) in a forearm blood flow (FBF) model.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Small-molecule discovery through DNA-encoded libraries.
   Peterson AA, Liu DR. · · 2023 · cited 145× · PMID 37328653 · DOI 10.1038/s41573-023-00713-6
2. Pharmacokinetics, pharmacodynamics and adverse event profile of GSK2256294, a novel soluble epoxide hydrolase inhibitor.
   Lazaar AL, Yang L, Boardley RL, Goyal NS, et al · · 2016 · cited 137× · PMID 26620151 · DOI 10.1111/bcp.12855
3. Epoxyeicosatrienoic Acids and 20-Hydroxyeicosatetraenoic Acid on Endothelial and Vascular Function.
   Imig JD. · · 2016 · cited 66× · PMID 27451096 · DOI 10.1016/bs.apha.2016.04.003
4. Mechanisms of Vascular Dysfunction in COPD and Effects of a Novel Soluble Epoxide Hydrolase Inhibitor in Smokers.
   Yang L, Cheriyan J, Gutterman DD, Mayer RJ, et al · · 2017 · cited 64× · PMID 27884766 · DOI 10.1016/j.chest.2016.10.058
5. The 2014 Bernard B. Brodie award lecture-epoxide hydrolases: drug metabolism to therapeutics for chronic pain.
   Kodani SD, Hammock BD. · · 2015 · cited 56× · PMID 25762541 · DOI 10.1124/dmd.115.063339
6. The role of epoxyeicosatrienoic acids in the cardiovascular system.
   Yang L, Mäki-Petäjä K, Cheriyan J, McEniery C, et al · · 2015 · cited 54× · PMID 25655310 · DOI 10.1111/bcp.12603
7. Epoxy Fatty Acids Are Promising Targets for Treatment of Pain, Cardiovascular Disease and Other Indications Characterized by Mitochondrial Dysfunction, Endoplasmic Stress and Inflammation.
   McReynolds C, Morisseau C, Wagner K, Hammock B. · · 2020 · cited 53× · PMID 32894508 · DOI 10.1007/978-3-030-50621-6_5
8. The Role of Cytochrome P450 Epoxygenases, Soluble Epoxide Hydrolase, and Epoxyeicosatrienoic Acids in Metabolic Diseases.
   Xu X, Li R, Chen G, Hoopes SL, et al · · 2016 · cited 42× · PMID 28140329 · DOI 10.3945/an.116.012245