PK study assessments
Blood samples for PK assessment were collected on Days 1, 2, 7, 8 and 9 (once or twice daily). On Day 10 (steady state) blood samples were collected pre-dose and at 20 min, 40 min, 1 h, 1 h 20 min, 1 h 40 min, 2 h, 2 h 20 min, 2 h 40 min, 3 h, 4 h, 6 h, 8 h and 12 h following QD and BID dosing and also at 16 h post dosing for the QD schedule. Plasma concentrations of MR309 were measured using a validated liquid chromatography–tandem mass spectrometry method.
Safety was assessed using 12-lead ECGs (monitored predose and on each study day with multiple assessments on Days 1 and 10), vital signs (monitored predose and at regular intervals during each study period), and AEs which were recorded throughout the study (coded per Medical Dictionary for Regulatory Activities [MedDRA] v18.1).
The primary objective was to compare the steady state PK of MR309 given QD and BID. The primary endpoints were area under the plasma concentration time curve from the time of dosing over one dosing interval (24 h QD or 12 h BID) at steady state (AUCtau), maximum plasma concentration at steady state (Cmaxss) and minimum plasma concentration at steady state (Cminss) for MR309. Secondary PK endpoints for MR309 included time to Cmaxss (tmaxss), fluctuation, and relative bioavailability (ratio of dose-corrected AUCtau values, and expressed as a percentage), Cmaxss ratio and Cminss ratio (calculated from derived parameters).