TABLE 2

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

Nintedanib 150 mgAdjusted gMean ratio+ % (90% CI)Intra-individual gCV %
Alone (reference)+ pirfenidone 801 mg (test)
Subjects n1712
Primary end-points
 AUC0-tz ng·h·mL−1169.7150.388.6 (65.4–120.0)45.1
 Cmax ng·mL−128.623.080.6 (51.3–126.8)74.6
Secondary end-point
 AUC0-∞ ng·h·mL−1195.6175.089.5 (66.3–120.7)44.3
Other end-points
 tmax h2.0 (0.5–6.0)2.5 (2.0–6.0)
 Half-life h9.3 (22.8)8.7 (30.0)
Sensitivity analyses
 AUC0-tz ng·h·mL−1169.7162.795.9 (69.9–131.5)§45.1
 Cmax ng·mL−128.626.592.8 (56.8–151.3)§75.0
 AUC0-∞ ng·h·mL−1195.6190.797.5 (71.7–132.5)§43.8

Data are presented as adjusted gMean, median (range) or gMean (gCV) (%), unless otherwise stated. gMean: geometric mean; gCV: geometric coefficient of variation; AUC0-tz: area under the plasma concentration–time curve from time 0 to time of the last quantifiable drug plasma concentration; Cmax: maximum observed plasma concentration; AUC0-∞: area under the concentration–time curve from time 0 extrapolated to infinity; tmax: time to reach Cmax. #: 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.