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The pharmacokinetics (PK) and safety of single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) after single and repeat dosing in healthy Chinese adults were assessed. In this open-label study (NCT02837380), subjects received once-daily FF/UMEC/VI 100/62.5/25 µg on day 1 and repeat doses on days 2-7. PK parameters (days 1 and 7) included maximum observed concentration (Cmax ) and area under the plasma concentration-time curve (AUC) from time zero (predose) to last time of quantifiable concentration (AUC0-t ). Terminal phase half-life (t½ ) on day 1 was estimated. The primary objective was to assess systemic exposure of FF 100 µg, UMEC 62.5 µg, and VI 25 µg following single-inhaler triple therapy on days 1 and 7. On day 1, geometric mean t½ of UMEC and VI was 0.36 and 0.52 hours, respectively; t½ of FF was not representative because of nonquantifiable concentration data. On days 1 and 7, geometric mean Cmax of FF was 10.46 and 27.32 pg/mL, respectively; Cmax of UMEC was 144.14 and 241.35 pg/mL, respectively; and Cmax of VI was 120.42 and 196.78 pg/mL, respectively. AUC0-t of FF was 1.77 and 276.96 pg·h/mL, respectively; AUC0-t of UMEC was 28.44 and 117.19 pg·h/mL, respectively; and AUC0-t of VI, 42.46 and 101.12 pg·h/mL, respectively. The PK of FF/UMEC/VI was as expected for the individual-component PK previously reported in healthy Chinese adults. No new safety signals were observed.

Control charts play an important role in Phase I studies, which are conducted to establish process control and generate reference data for parameter estimation and calculation of prospective (Phase II) control limits. Researchers have tabulated the necessary charting constants for the normal theory–based Phase I Shewhart X¯ chart for the process mean to achieve a desired nominal false alarm probability given the number of Phase I subgroups, m, up to 15. However, in practice, when parameters are estimated, the currently recommended number of Phase I subgroups is much larger than covered by their tables. Recognizing the need and taking advantage of some recently available software and computing resources, an extension to these tables is provided for m = 3(1)10 , 15(5)30 , 50(25)300 and n = 3 , 5 , 7 , 10. In addition to the tables, an R program is provided to calculate the charting constant, on demand, for user-given values of nominal false alarm probability, m, and n. An appendix shows the details of how the program should be used.