GFT505 Efficacy and Safety in Healthy Volunteers and Patients Suffering from Atherogenic Dyslipidemia

GFT505 Efficacy and Safety in Healthy Volunteers and Patients Suffering from Atherogenic Dyslipidemia GFT505 is a drug candidate fo GFT505 is a drug candidate for the treatment of metabolic disorders notably atherogenic dyslipidemia associated with metabolic syndrome and Type II diabetes. GFT505 and GFT1007, its main active circulating metabolite, activate PPAR[alpha] and PPAR[delta] subtypes. GFT505 potently reduces plasma triglycerides and total cholesterol and potently increases HDL cholesterol in animal models of dyslipidemia. GFT505 prevents the development of atherosclerotic plaques and has insulin sensitizing properties in mice. Efficacy and safety data obtained with GFT505 in human are presented.[br]In healthy volunteers treated for 14 days with increasing doses, GFT505 was well tolerated with no clinically relevant emergent adverse event. The MTD in human has not been reached while reduction in plasma triglycerides and increase in HDL-C was observed from 40 to 100 mg/d. The safety of GFT505 was confirmed in two distinct phase IIa trials. Pharmacokinetic analysis demonstrated a linear dose-exposure relationship for GFT505 and GFT1007. The food-effect study revealed that a high fat breakfast did not modify kinetics of GFT505 and GFT1007.[br]In a double blind, placebo controlled phase IIa trial conducted in 98 patients with atherogenic dyslipidemia (high triglycerides, low HDL-C), treatment with GFT505 at 80 mg/day for 28 days led to a 21 % (p=0.0027 vs placebo) reduction in triglycerides and a 9 % (p=0.003 vs placebo) increase in HDL-C. GFT505 significantly reduced ApoCIII (-17 %, p=0.04) and ApoB (-7 %, p=0.02), increased ApoAI (+6%, p=0.002) and ApoAII (+15 %, p[lt]0.0001) and reduced fibrinogen and haptoglobin. These effects are comparable to those reported with fibrates such as fenofibrate in this population. In contrast, GFT505 did not induce clinically significant effects on homocysteine and creatinine. Finally, GFT505 reduced two distinct indicators of liver dysfunction: alanine aministransferase (ALAT, -15 % vs placebo, p=0.02) and Gamma Glutamyl Transpeptidase (-20 % vs placebo) while it did not affect plasma levels of aspartate aminotransferase.[br]These first clinical trials position GFT505 as a new efficient and safe drug candidate for the treatment of atherogenic dyslipidemia of (pre)diabetes. REMY HANF, RAPHA[Euml]L DARTEIL, DEAN W. HUM, BART STAELS 677-P Loos, France, Lille, France Pharmacologic Treatment of Diabetes or its Complications