Pharmacokinetic outcomes: PK study
MR309 200 mg BID dosing was associated with lower geometric mean (CV,
%) Cmaxss (4143 [17.2] ng/mL vs 5222 [18.3] ng/mL) and higher
Cminss (1915 [29.8] ng/mL vs 1764 [29.9] ng/mL) compared with
400 mg QD dosing (Table 2; Figure 2). Bioavailability comparisons
yielded geometric mean ratios (BID/QD dosing) of 79.3% (90% CI 73.5,
85.7%) and 108.5 (90% CI 104.6, 112.6%) for Cmaxss and Cminss,
respectively. Correspondingly, less fluctuation was observed with BID
dosing (mean 87% [SD 22%]) compared with the QD regimen (145%
[49%]; Table 2). The ratio of dose-adjusted AUCtau (BID/QD dosing)
indicated broadly equivalent bioavailability across the two dosing
schedules (107% [90% CI 103, 111.5]).