TABLE 3

Pharmacokinetic parameters of pirfenidone after multiple oral administration of 801 mg pirfenidone three times daily alone (reference), and together with steady-state nintedanib 150 mg twice daily (test)#

Pirfenidone 801mg three times dailyAdjusted gMean ratio+ % (90% CI)Intra-individual gCV %
Alone (reference)+ nintedanib 150mg twice daily (test)
Subjects n1513
Primary end-points
 AUCτ,ss ng·h·mL−140 20039 00097.2 (87.8–107.5)14.1
 Cmax,ss ng·mL−110 60010 50099.5 (87.9–112.6)17.4
Other end-points
 tmax,ss h1.00 (0.5–3.0)1.00 (0.5–4.0)
Sensitivity analysis
 AUCτ,ss ng·h·mL−140 50038 50095.2 (85.9–105.5)§14.1
 Cmax,ss ng·mL−110 70010 40097.2 (85.6–110.4)§17.5

Data are presented as adjusted gMean or median (range). gMean: geometric mean; gCV: geometric coefficient of variation; AUCτ,ss: area under the plasma concentration–time curve over a dosing interval τ at steady-state; Cmax,ss: maximum measured plasma concentration at steady-state; tmax,ss: time to reach Cmax,ss. #: in pharmacokinetic population; : gMean ratio adjusted for “treatment” as a fixed effect; “subject” was considered as a random effect; +: ratio of test/reference; §: gMean ratio adjusted for “treatment” and “subject” as fixed effects.