An Open-label Single Dose Randomized, Parallel Group Study Followed by Single-blind Repeat Dosing, to Compare the Relative Bioavailability of GSK2212836

Sixteen healthy subjects will be randomized to each of the 3 parallel treatment groups. Eligible subjects will check in to the clinical unit on Day -2 and have 24-hr pharmacokinetic collections on Day -1 and on Day 1. Once the pharmacokinetic parameters of the formulations have been analyzed, doses of GSK2212836 will be selected for further study in Part B. Subjects from Part A will participate in Part B.
Part B is a single blind, randomized, placebo controlled study that will consist of a 2-week repeat dose period with 3 dose levels and one dose of the marketed formulation of GSK2212836. Subjects will check in to the clinical unit on Day -3; will participate in a test meal on Day -2 and have 24-hr baseline pharmacokinetic profiles on Day -1 and Day 1. Subjects will be released from the clinic on Day 2, and return for daily dosing on Days 3 through 12. On Day 6, they will also have a brief outpatient visit. Subjects will check into the clinic again on the evening of Day 12, and on Day 13 they will again have 24-hr pharmacokinetic profiles collected. Subjects will be released from the clinical research unit on Day 14, following a test meal, triglyceride sampling and check-out assessments, and will be released from the study 5-10 days later after completing a follow up visit.

开始日期2009-10-15

申办/合作机构

GSK Plc

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项与 Doconexent ethyl/Icosapent ethyl 相关的文献（医药）

2017-01-01·Biomedicine & Pharmacotherapy2区 · 医学

Effect of dietary n-3 fatty acids supplementation on fatty acid metabolism in atorvastatin-administered SHR.Cg-Lepr/NDmcr rats, a metabolic syndrome model

2区 · 医学

Article

作者: Tanabe, Yoko ; Tsuchikura, Satoru ; Hashimoto, Michio ; Hossain, Shahdat ; Al Mamun, Abdullah ; Katakura, Masanori ; Shido, Osamu

The effects of cholesterol-lowering statins, which substantially benefit future cardiovascular events, on fatty acid metabolism have remained largely obscured. In this study, we investigated the effects of atorvastatin on fatty acid metabolism together with the effects of TAK-085 containing highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl ester on atorvastatin-induced n-3 polyunsaturated fatty acid lowering in SHR.Cg-Lepr^cp/NDmcr (SHRcp) rats, as a metabolic syndrome model. Supplementation with 10mg/kg body weight/day of atorvastatin for 17 weeks significantly decreased plasma total cholesterol and very low density lipoprotein cholesterol. Atorvastatin alone caused a subtle change in fatty acid composition particularly of EPA and DHA in the plasma, liver or erythrocyte membranes. However, the TAK-085 consistently increased both the levels of EPA and DHA in the plasma, liver and erythrocyte membranes. After confirming the reduction of plasma total cholesterol, 300mg/kg body weight/day of TAK-085 was continuously administered for another 6 weeks. Supplementation with TAK-085 did not decrease plasma total cholesterol but significantly increased the EPA and DHA levels in both the plasma and liver compared with rats administered atorvastatin only. Supplementation with atorvastatin alone significantly decreased sterol regulatory element-binding protein-1c, Δ5- and Δ6-desaturases, elongase-5, and stearoyl-coenzyme A (CoA) desaturase-2 levels and increased 3-hydroxy-3-methylglutaryl-CoA reductase mRNA expression in the liver compared with control rats. TAK-085 supplementation significantly increased stearoyl-CoA desaturase-2 mRNA expression. These results suggest that long-term supplementation with atorvastatin decreases the EPA and DHA levels by inhibiting the desaturation and elongation of n-3 fatty acid metabolism, while TAK-085 supplementation effectively replenishes this effect in SHRcp rat liver.

2015-02-01·Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

n-3 fatty acids effectively improve the reference memory-related learning ability associated with increased brain docosahexaenoic acid-derived docosanoids in aged rats

Article

作者: Makoto Arita ; Michio Hashimoto ; Takayuki Inoue ; Shahdat Hossain ; Yoko Tanabe ; Masanori Katakura ; Osamu Shido ; Abdullah Al Mamun

We investigated whether a highly purified eicosapentaenoic acid (EPA) and a concentrated n-3 fatty acid formulation (prescription TAK-085) containing EPA and docosahexaenoic acid (DHA) ethyl ester could improve the learning ability of aged rats and whether this specific outcome had any relation with the brain levels of EPA-derived eicosanoids and DHA-derived docosanoids. The rats were tested for reference memory errors (RMEs) and working memory errors (WMEs) in an eight-arm radial maze. Fatty acid compositions were analyzed by GC, whereas brain eicosanoid/docosanoids were measured by LC-ESI-MS-MS-based analysis. The levels of lipid peroxides (LPOs) were measured by thiobarbituric acid reactive substances. The administration of TAK-085 at 300 mg·kg⁻¹day⁻¹ for 17 weeks reduced the number of RMEs in aged rats compared with that in the control rats. Both TAK-085 and EPA administration increased plasma EPA and DHA levels in aged rats, with concurrent increases in DHA and decreases in arachidonic acid in the corticohippocampal brain tissues. TAK-085 administration significantly increased the formation of EPA-derived 5-HETE and DHA-derived 7-, 10-, and 17-HDoHE, PD1, RvD1, and RvD2. ARA-derived PGE2, PGD2, and PGF2α significantly decreased in TAK-085-treated rats. DHA-derived mediators demonstrated a significantly negative correlation with the number of RMEs, whereas EPA-derived mediators did not exhibit any relationship. Furthermore, compared with the control rats, the levels of LPO in the plasma, cerebral cortex, and hippocampus were significantly reduced in TAK-085-treated rats. The findings of the present study suggest that long-term EPA+DHA administration may be a possible preventative strategy against age-related cognitive decline.

2013-11-01·Journal of Clinical Lipidology2区 · 医学

Long-term safety and efficacy of TAK-085 in Japanese subjects with hypertriglyceridemia undergoing lifestyle modification: The omega-3 fatty acids randomized long-term (ORL) study

2区 · 医学

Article

作者: Ichiro Tatsuno ; Kentarou Kudou ; Yasushi Saito ; Jun Ootake

BACKGROUNDTAK-085 is an omega-3 preparation that contains eicosapentaenoic acid ethyl-ester (EPA-E) and docosahexaenoic acid-ethyl ester used in the management of hypertriglyceridemia.OBJECTIVEThe aim of the study was to evaluate the long-term safety (adverse events [AEs], laboratory parameters, vital signs, weight, and electrocardiograms) and effects on lipid profiles, especially triglyceride levels, of TAK-085 in Japanese patients with hypertriglyceridemia (triglyceride levels ≥150 mg/dL and <750 mg/dL).METHODSIn this multicenter, open-label, randomized study, adults with hypertriglyceridemia undergoing lifestyle modification received TAK-085 2 g (2 g once daily; n = 165) or 4 g (2 g twice daily; n = 171), or EPA-E 1.8 g (0.6 g three times daily; n = 167) for 52 weeks. Patients were stratified for co-administration of a statin.RESULTSTAK-085 was well tolerated throughout the 52-week study. Overall, no substantial differences were found in the tolerability of TAK-085 2 g, TAK-085 4 g, and EPA-E 1.8 g with incidence rates for AEs of 83.6%, 86.0%, and 89.2%, respectively. Most AEs were mild or moderate in severity. Triglyceride levels decreased from baseline in all groups by week 4, and the decreases were maintained throughout the study. At week 52 the reduction in triglycerides with TAK-085 2 g (-13.9%) was similar to that with EPA-E 1.8 g (-12.1%), whereas the reduction seen with TAK-085 4 g (-25.5%) was greater than that with EPA-E 1.8 g, as assessed by point estimates and 95% confidence intervals.CONCLUSIONSTAK-085 was safe and well tolerated for up to 52 weeks of treatment in Japanese patients with hypertriglyceridemia undergoing lifestyle modification. Reductions in triglyceride levels achieved after 4 weeks were maintained at 52 weeks.

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