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.