PGx7664: Exploratory PGx evaluation of ALT elevations observed in subjects treated with GSK2881078 (SARM) from study 204699

Trial description: GSK2881078 is a non-steroidal selective androgen receptor modulator (SARM), and in development for treatment of muscle weakness due to chronic illness in elderly. Elevations in alanine aminotransferase (ALT) were observed in study 204699, which was a phase I study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the repeat doses of GSK2881078 in healthy subjects between 50 and 75 years of age. Approximately 34% (21/62) of subjects treated with GSK288107 had maximum on treatment ALTs >=2 time of upper limit of normal (ULN), with 14.5% (9/62) having ALT levels >=3 times of ULN, and one female subject with an ALT >=5 times of ULN withdrawn from the study. No bilirubin elevation was observed in the subjects from 204699.Genetic risk factors for drug-induced liver injury have been identified for some marketed medicines and investigational products. These genetic variants primarily fall into two categories – those located in genes associated with drug metabolism and in genes associated with immune response, e.g. human leukocyte antigen (HLA) alleles associated with drug-induced liver injury (HLA-A*33:03 for ticlopidine, HLA-DRB1*15:01 for amoxicillin-clavulanate and lumiracoxib, HLA-DRB1*07:01 for ximelagatran and lapatinib, and HLA-B*57:01 for flucloxacillin and pazopanib).The 207523 study objective is to conduct an assessment on the effect of HLA alleles, cytochrome P450 3A4 (CYP3A4) and genome-wide variation on ALT elevation in subjects treated with GSK2881078 from study 204699 Part A.