The trial included MI patients who carry at-risk variants in the FLAP gene or in the leukotriene A4 hydrolase gene. Of 268 patients screened, 191 were carriers of at-risk variants in FLAP (87 percent) or leukotriene A4 hydrolase (13 percent). Individuals were enrolled in April 2004 and were followed up by designated cardiologists from the Landspitali University Hospital in Iceland until September 2004. Patients were first randomized to receive 250 mg/d of DG-031, 500 mg/d of DG-031, 750 mg/d of DG-031, or placebo. After a 2-week washout period, patients received DG-031 if they had received placebo first or placebo if they had received DG-031 first. Treatment periods lasted for 4 weeks.
The researchers found that levels of several biomarkers linked to arterial inflammation and risk of MI decreased. In response to 750 mg/d of DG-031, production of leukotriene B4 was significantly reduced by 26 percent and myeloperoxidase was significantly reduced by 12 percent. The higher 2 doses of DG-031 produced a nonsignificant reduction in C-reactive protein (16 percent) at 2 weeks. However, there was a more pronounced reduction (25 percent) in C-reactive protein at the end of the washout period that was significant and persisted for another 4 weeks thereafter. An 8-day, open-label follow-up study with 75 patients with the same genetic and disease profile as in the Phase IIa was conducted to further examine the effect of DG031 on CRP and myeloperoxidase. The results of this study showed that the 750mg/d dose of DG031, when administered as 250 mg 3 times daily resulted in a 38 percent reduction in CRP levels, as well as a 31 percent reduction in myeloperoxidase levels measured 6 hours after dosing on day 8. In both studies, the FLAP inhibitor DG-031 was well-tolerated and was not associated with any serious adverse events.
"When taken together, the data from our MI gene-isolation study and the clinical trial reported herein show that DG-031 is a safe and w
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