Table 1.

Zanubrutinib clinical study data used in PBPK model development and verification.

Clinical study	Population	Study description		Dose regimen	PK data used in PBPK model
BGB−3111–104 4 (NCT03301181)	Healthy volunteer	Clinical DDI study with strong CYP3A inhibitor/inducer		20 mg q.d. (DDI with itraconazole, n = 18)	Development
				320 mg (DDI with rifampicin, n = 20)	Verification
BGB−3111–108 5 (NCT03561298)	Healthy volunteer	Effects of zanubrutinib on substrates of CYP3A, CYP2C9, CYP2C19, P‐gp and BCRP		2 mg midazolam (n = 18)	Development
				160 mg b.i.d. dose (n = 17) b.i.d. Days 1–7	Verification
BGB−3111–106 38 (NCT03432884)	Healthy volunteer	A thorough QTc study		160 mg (n = 28) Single dose	Verification
BGB−3111–107 39 (NCT03465059)	Healthy volunteer	A hepatic impairment study		80 mg (n = 11) Single dose	Verification
BGB−3111–AU−003 3 (NCT02343120)	B‐cell malignancy	Phase 1/2 dose escalation and expansion study		40 mg q.d. (n = 4) 80 mg q.d. (n = 5) 160 mg q.d. (n = 6) 320 mg q.d. (n = 22) 160 mg b.i.d. (n = 72) q.d. Days 1–8 b.i.d. Days 1–8	Verification

Abbreviations: b.i.d., twice daily; DDI, drug‐drug interaction; PBPK, physiologically based pharmacokinetics; q.d., once daily.