Jan 16, 2012 16:18: Andrés Martínez changed "Field" from "Other" to "Medical" , "Field (specific)" from "Chemistry; Chem Sci/Eng" to "Medical (general)"

Jan 27, 2012 16:28: Yana Dovgopol changed "Term Context" from "Three cases of increase in ALT above 2 times the upper limit of normal (ULN) have been reported. One case after 7 days of 0.25 mg RO4917523, with a peak value 4*ULN ten days after the treatment onset. One case after two single doses of 1 mg RO4917523 MR or IR fasted separated by a wash-out period of 21 days. ALT was markedly raised (>2*ULN) from Day 36 to Day 50 post-dose and peaked at 6.3*ULN on Day 43 post-dose. AST and ALT remained between 2*ULN and above ULN until Day 156 post-dose. Total bilirubin, gamma glutamyltransferase (GGT) and alkaline phosphatase remained within the normal ranges at all time points. Alcohol breath tests, serodiagnostics (hepatitis A, B and C, CMV, EBV and Herpes viruses, Toxoplasma), anti-nuclear antibodies (ANA) and hepatic ultrasound were all negative. The subject confessed to the occasional use of steroids for weight lifting. One case after one 1 mg RO4917523 IR fasted single dose where ALT increase started to be noticed 9 days after dosing with a minimal elevation in ALT at 1.02*ULN and which continued to increase 20 days post-dose with an ALT value of 1.66*ULN when he was withdrawn from the study. This subject had no known history of alcohol abuse and the alcohol breath tests were negative at all measured time points. The IgM for hepatitis A, B and C were negative. CMV IgG and IgM were negative. Regarding Epstein-Barr virus, the VCA antibody IgM and IgG were negative whilst EBNA IgG was positive, which excludes an acute infection. HSV type 1 IgG and HSV type 1 and 2 IgM antibodies were positive but HSV type 2 IgG antibodies were negative. This is indicative of an ongoing infection either primary or a reactivation. Toxoplasma IgG was negative. ANA, smooth muscle, transglutaminase, reticulin, endomysial and anti-gliad antibodies were all negative, excluding an auto-immune disease. The hepatic ultrasound was normal. ALT value increased up to a value of 2.08*ULN 22 days post-dose It then decreased to ULN 57 days post-dose. ALT value increased again up to 1.7*ULN 71 days post-dose after the subject had an episode of respiratory infection and returned then within normal ranges 112 days post-dose. In the three cases, alkaline phosphatase, GGT, total bilirubin and CPK levels were at all times normal. muchas gracias!!!" to "muchas gracias!!!"