A Phase I Study Allowing Clinical Screening Of Multiple Solubility-Enhancement Formulation Technologies

BOS172767 is a first in class small molecule inverse agonist of retinoic acid-related orphan nuclear receptor gamma-t, being developed for the treatment of autoimmune diseases. Safety and tolerability have been demonstrated in a previous first in human (FIH) Phase 1 study using a simple API blend in capsule.

Low oral exposure, non-linear pharmacokinetics (PK), high variability and a large positive food effect were observed. Therefore, a solubility enhanced formulation was considered necessary to help overcome these PK challenges and identify a formulation suitable for long-term clinical development.

Formulations were developed and screened using an integrated platform of real-time adaptive GMP manufacturing and clinical testing. The study was designed to assess the clinical performance of three prototype formulations, assess food effect and dose linearity of a selected formulation and also the impact on exposure in subjects taking proton pump inhibitors (PPI). The clinical PK data generated in the study would then be utilized to select a formulation for further development.