TABLE 3

Summary of geometric mean PK parameters of acalabrutinib and total 14C radioactivity in healthy human subjects after 100 mg oral and ≤10 µg intravenous doses

Values are presented as geometric means (%CV) unless otherwise indicated.

ParameterAcalabrutinib
Oral Dose Cohort 1 
(n = 8)[14C]Acalabrutinib
Intravenous Dose Cohort 1 (n = 8)cAcalabrutinib
Plasma Cohort 2 
(n = 6)Total 14Cd
Plasma Cohort 2 
(n = 6)Whole Blood Cohort 2 (n = 6)
Cmax (ng/ml)639 (53.8)510 (56.3)305 (44.0)1340 (34.4)1060 (31.3)
Tmax (h)a0.50 (0.50–0.75)0.075 (0.033–0.117)0.5 (0.5–0.517)0.875 (0.750–2.00)0.750 (0.750–2.00)
AUC0–t (ng⋅h/ml)643 (39.7)201 (32.6)386 (39.2)5930 (29.4)11,500 (27.1)
AUC0–12 h (ng⋅h/ml)642 (35.9)199 (30.2)406 (36.6)4390 (29.4)3760 (29.6)
AUC0–168 h (ng⋅h/ml)NDND407 (36.6)6250 (24.9)11,500 (27.1)
AUC0–∞ (ng⋅h/ml)643 (35.7)199 (30.2)407 (36.6)6410 (25.1)ND
t1/2 (h)1.57 (0.600)1.78 (0.461)1.47 (0.45)46.5 (21.8)395 (9.6)e
CL or CL/F (l/h)163 (35.7)39.4 (30.6)246 (36.6)NDND
Vz or Vz/F (l)344 (36.2)98.0 (42.8)499 (36.1)NDND
Vss (l)ND34.2 (40.2)NDNDND
F (%)b25.3 (14.3)NANANANA
Acalabrutinib/total 14C AUC(0–∞) ratioNDNDNA0.0635 (17.8)NA
Renal CL (l/h)1.21 (32.8)0.654 (55.6)1.33 (36.0)NDND
Cumulative %feu (%)0.759 (28.3)1.69 (45.7)0.519 (56.5)NDND
  • %feu, percent excreted in urine over the entire sample collection period; F, bioavailability fraction of dose absorbed relative to intravenous dosing expressed as a percentage; NA, not applicable; ND, not determined; Vss, volume of distribution at steady state; Vz, volume of distribution based on the terminal phase.

  • a Values are the median (minimum–maximum).

  • b Absolute bioavailability was calculated using the dose-normalized AUC0–∞ after oral and intravenous administration due to differing doses with each route of administration, according to the following equation: F = [AUC0–∞ (oral)/AUC0–∞ (intravenous)]/[dose (intravenous)/dose (oral)].

  • c Units are (pg Eq/ml) or (pg Eq⋅h/ml).

  • d Units are (ng Eq/ml) or (ng Eq⋅h/ml).

  • e n = 5. Half-life value is greater than two times the sampling interval.