Cohort 1 | Cohort 2 | Cohort 3 | |||||||
Patients without/with ongoing pirfenidone therapy | Alone | With nintedanib 50 mg twice daily | Patients without/with ongoing pirfenidone therapy | Alone | With nintedanib 100 mg twice daily | Patients without/with ongoing pirfenidone therapy | Alone | With nintedanib 150 mg twice daily | |
After breakfast | |||||||||
AUC0–4,ss h·ng·mL−1 | 4/4 | 34 400 (36.3) | 34 300 (39.9) | 3/3 | 45 800 (26.6) | 35 000 (32.2) | 9/7 | 32 500 (21.2) | 35 900 (21.8) |
Cmax,ss ng·mL−1 | 4/4 | 11 900 (28.9) | 12 800 (44.3) | 4/3 | 14 600 (41.5) | 15 300 (51.1) | 9/8 | 11 200 (26.6) | 12 600 (27.2) |
tmax,ss h | 4/4 | 1.6 (1.0–3.0) | 0.7 (0.5–2.0) | 4/3 | 1.5 (0.5–3.0) | 2.0 (0.5–2.0) | 9/8 | 1.1 (0.5–3.0) | 0.8 (0.5–3.9) |
RAUC0–4,ss,T/R | 0/4 | 1.0 (32.2) | 0/2 | 0.7 (51.8) | 0/7 | 1.1 (13.1) | |||
RCmax,ss,T/R | 0/4 | 1.1 (45.1) | 0/3 | 1.0 (38.6) | 0/8 | 1.1 (12.4) | |||
After lunch | |||||||||
AUC0–8,ss h·ng·mL−1 | 4/4 | 72 800 (40.7) | 71 000 (40.8) | 3/3 | 84 100 (11.4) | 71 500 (19.1) | 8/6 | 60 900 (22.9) | 63 600 (27.7) |
Cmax,ss ng·mL−1 | 4/4 | 14 600 (20.9) | 12 000 (37.3) | 4/3 | 15 100 (19.5) | 12 100 (10.7) | 9/8 | 12 900 (30.2) | 12 500 (23.0) |
tmax,ss h | 4/4 | 1.0 (0.5–3.1) | 2.5 (1.0–3.9) | 4/3 | 2.0 (1.0–3.0) | 4.0 (2.0–4.0) | 9/8 | 1.0 (0.4–6.0) | 2.0 (0.5–4.4) |
t1/2,ss h | 4/3 | 3.4 (50.5) | 4.0 (31.7) | 4/1 | 3.5 (49.0) | 3.6 (NC) | 8/5 | 3.1 (40.6) | 3.2 (39.1) |
RAUC0–8,ss,T/R | 0/4 | 1.0 (4.7) | 0/2 | 0.9 (21.2) | 0/5 | 1.0 (14.6) | |||
RCmax,ss,T/R | 0/4 | 0.8 (19.7) | 0/3 | 0.8 (20.2) | 0/8 | 0.9 (25.6) | |||
AUC0–12,ss# h·ng·mL−1 | 4/4 | 10 8000 (36.8) | 105 000 (40.3) | 3/3 | 130 000 (16.0) | 107 000 (22.4) | 8/6 | 92 000 (18.3) | 102 000 (22.2) |
RAUC0–12,ss,T/R | 0/4 | 1.0 (9.9) | 0/2 | 0.8 (30.8) | 0/5 | 1.1 (12.2) |
Data are presented as n, geometric mean (geometric coefficient of variation %) or median (range). AUCt1–t2,ss: area under the concentration–time curve of the analyte in plasma at a steady state over the time interval from t1 to t2; Cmax,ss: maximum concentration of the analyte in plasma at steady state over a uniform dosing interval τ; tmax,ss: time from dosing to maximum concentration of the analyte in plasma at steady state over a uniform dosing interval τ; RAUCt1–t2,ss,T/R: ratio of AUCt1–t2,ss of the test treatment to AUCt1–t2,ss of the reference treatment; RCmax,ss,T/R: ratio of Cmax,ss of the test treatment to Cmax,ss of the reference treatment; t1/2,ss: terminal half-life of the analyte in plasma at steady state. #: AUC0–12,ss=AUC0–4,ss (post-dose after breakfast)+AUC0–8,ss (post-dose after lunch). NA: not applicable; NC: not calculated.