Date: 2012-05-04
Type of information:
phase: 2
Announcement: results
Company: Genfit (France)
Product: GFT505
Action mechanism:
Disease: NAFLD (non-alcoholic fatty liver disease)
NASH (non-alcoholic steatohepatitis)
Therapeutic area: Metabolic diseases - Liver diseases
Country:
Trial
details: One of the objectives of the phase I trial, GFT505-111-7 was to assess the safety, tolerability and pharmacokinetics of increasing daily doses of GFT505 (120, 180 and 240 mg/day) administered for 14 days in overweight or obese volunteers.
According to the protocol, 12 subjects were included in each of the three consecutive cohorts (9 treated with GFT505 + 3 placebo) corresponding to the three dose levels. Decision to escalate to the next dose was taken after reviewing complete blinded safety and PK data collected from Day 1 to Day 15: AEs, ECG, vital signs, laboratory tests and PK results.
Latest
news: * On May 4, 2012, Genfit, a biopharmaceutical company at the forefront of drug discovery and development, focusing on the early diagnosis and preventive treatment of cardiometabolic and associated disorders, has announced the results of the GFT505-111-7** study demonstrating the safety and efficacy of increasing doses of GFT505 up to a dose three-fold higher than the current therapeutic dose of 80 mg/d.
Safety of GFT505 up to 240 mg/d:
The primary aim of the GFT505-111-7 study was to demonstrate the safety of GFT505 in obese subjects at doses higher than the current therapeutic dose of 80 mg/d used in all Phase IIa proof-of-concept studies to date. GFT505 was thus administered for 14 days at 120 mg/d, 180 mg/d, and 240 mg/d, and the results compared to those obtained under placebo.
No serious adverse event was reported in this study. Compared to placebo, there were fewer undesirable effects in GFT505-treated patients. Moreover, no adverse event was reported in the subjects treated at the dose of 240 mg/d. In all groups, biochemical safety markers were unchanged. In particular, renal safety markers (creatinine) and hematological parameters were unchanged by GFT505 treatment.
Efficacy markers up to 240 mg/d:
At all tested doses, there were strong beneficial effects on markers of hepatic dysfunction (ALP, ALT, AST and GGT). For example, at the dose of 240 mg/d, the change in GGT levels following GFT505 treatment was -22.9±4.8% (p=0.001) vs +23.2±11% (p=0.06) in the placebo group. Similarly, the change in alkaline phosphatase (ALP) levels was -18.1±1.5% (p<0.0001) vs +13.6±5.4% (p=0.03) in the placebo group. For the first time, a significant decrease in the level of bilirubin was observed under GFT505 treatment (-23.2±8.9 %, p=0.03 at 240 mg/d vs -5.4±6.8%, p=0.44 under placebo), providing further proof of the liver-protective potential of GFT505.
In parallel, at all tested doses, GFT505 strongly improved plasma lipid parameters, with a decrease in the level of triglycerides (-22.4±8.1%, p=0.02 at 240 mg/d vs +19.8±8.2%, p=0.04 under placebo) and above all a strong decrease in the level of total cholesterol (-20.5±2.8%, p<0.0001 at 240 mg/d vs +3.7±1.8%, p=0.08 under placebo) and LDL-cholesterol (-28.7±4.1%, p=0.0001 at 240 mg/d vs +4.1±4.9%, p=0.42 under placebo). Finally, in the GFT505-treated groups, there was a significant decrease in glycemia (-8.4±2.0%, p=0.002 at 240 mg/d vs -2.0±3.5%, p=0.58 under placebo), while inflammatory markers such as haptoglobin were also strongly decreased (-25.9±5.9%, p=0.0022 at 240 mg/d vs +6.2±6.5%, p=0.36 under placebo).
