Data and statistical analysis (PK study and PET study)
The data and statistical analysis comply with the recommendations of the British Journal of Pharmacology on experimental design and analysis. (Curtis et al., 2018)
In both studies, PK parameters were calculated using Phoenix WinNonlin version 6.2 or later (Certara L.P., Princeton, NJ, US) and statistical analyses were performed using SAS® version 9.3 or later (SAS Institute, Cary, NC, USA). The PK population comprised all subjects who received ≥1 dose of MR309 and provided data for at least 1 PK measurement while the safety population included all subjects who received at ≥1 dose of MR309.
Formal sample size calculations were not performed for either of these exploratory studies. Recruitment of 16 individuals was planned for the PK study, anticipating PK data would then be available from ≥12 subjects completing the study. A sample size of up to 8 participants (1 or 2 individuals per cohort) was planned for the PET study.
Safety parameters were described using summary statistics. Differences in PK parameters between QD and BID dosing schedules were assessed using an ANOVA model which included fixed terms for treatment regimen (QD or BID), sequence, period, and subject within the treatment sequence. PK parameters were not summarized by cohort or dose level in the PET study due to the small sample size. PET data analysis was performed by Imanova Ltd. (London, UK) using in-house MIAKATTM software (version 4.2.6.1), implemented using MATLAB (The Mathworks Inc. Natick, MA, US).
Both studies were conducted in accordance with the Declaration of Helsinki, International Conference on Harmonization Guidelines for Good Clinical Practice and the European Union Clinical Trials Directive. Procedures were approved by local ethics committees, and all subjects provided informed, written consent.