Poxel, a biopharmaceutical company, has commenced part two of the phase 1a study for PXL065, a deuterium-stabilised R-stereoisomer of pioglitazone intended for the treatment of non-alcoholic steatohepatitis (NASH), it was reported yesterday.

This second part of the Phase 1a study will enrol six healthy patients per group, with a primary aim to evaluate safety and tolerability and a secondary objective to assess dose proportionality.

This Phase 1a trial, which was discussed with the United States Food and Drug Administration in a pre-Investigational New Drug Application meeting, was designed to include two single oral doses and potentially up to three additional doses of PXL065. In Part one of the Phase 1a study, which was presented during the 2018 American Association for the Study of Liver Diseases (AASLD) meeting, twelve healthy subjects received a single oral dose of 22.5mg PXL065 or 45mg Actos. In this study, the product was indicated to be safe and well-tolerated with no adverse events. Based on the pharmacokinetic results, modelling predicts that a 15mg dose of PXL065 may provide a similar exposure of R-pioglitazone as a 45mg dose of the parent drug, pioglitazone (Actos), which suggests it should indicate similar efficacy with an improved safety profile, including reduced weight gain and fluid retention.

Pioglitazone is a drug approved for the treatment of type 2 diabetes that has demonstrated therapeutic efficacy for NASH, even in patients with advanced fibrosis.