This study will evaluate the effect of fluconazole and isavuconazole on the PK of acalabrutinib and its active metabolite, ACP-5862.
This is a 2-period study. On Day 1 of Period 1, all participants will be randomized to 1 of 2 treatment sequences and will receive a single oral dose of 100 mg acalabrutinib (Treatment A). In Period 2, the participants who participated in Period 1 will receive either Treatment B (fluconazole) or Treatment C (isavuconazole). In Period 2 Treatment B, participants will receive a single oral loading dose of 400 mg fluconazole on Day 1 one hour before a single oral dose of 100 mg acalabrutinib. In Period 2 Treatment C, participants will receive oral dose of 200 mg isavuconazole three times daily (TID; approximately 8 hours apart) on Day 1 and 200 mg isavuconazole once daily (QD) from Day 2 to Day 5 with a single oral dose of 100 mg acalabrutinib coadministered on Day 5. There will be a washout of at least 8 days between Period 1 and first dose in Period 2. All participants will return to the study site approximately 7 days after the last study drug for follow-up procedures and adverse event.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Modify as "Participants will receive a single oral dose of 100 mg (1 X 100 mg capsule) acalabrutinib either on Day 1 of Period 1 (Treatment A) and Day 1 of Period 2 (Treatment B) or Day 5 of Period 2 (Treatment C).
Participants will receive 400 mg fluconazole (2 × 200 mg tablets) on Day 1 Period 2 (Treatment B).
Participant will receive oral dose of 200 mg isavuconazole (2 × 186 mg of isavuconazonium sulfate capsules) three times daily on Day 1 and 200 mg isavuconazole (2 × 186 mg of isavuconazonium sulfate capsules) once daily on Days 2 to 5 in Period 2 (Treatment C).
Celerion
Tempe, Arizona, United States
Area Under the Plasma Concentration-time Curve to the Last Observed Nonzero Concentration (AUC0-t) of Acalabrutinib and ACP-5862
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)
Area Under the Plasma Concentration-time Curve to Infinity (AUC0-inf) of Acalabrutinib and ACP-5862
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)
Maximum Observed Plasma Concentration (Cmax) of Acalabrutinib and ACP-5862
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)
Percent of Area Under the Plasma Concentration-time Curve to Infinity Extrapolated (AUC%extrap) of Acalabrutinib and ACP-5862
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)
Time of the Maximum Observed Plasma Concentration (Tmax) of Acalabrutinib and ACP-5862
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)
Time of the Last Measurable Nonzero Plasma Concentration (Tlast) of Acalabrutinib and ACP-5862
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)
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Apparent Terminal Elimination Half-life (T1/2) of Acalabrutinib and ACP-5862
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)
Apparent Terminal Elimination Rate Constant (Kel) of Acalabrutinib and ACP-5862
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)
Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Acalabrutinib
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)
Apparent Volume of Distribution During the Terminal Elimination Phase After Oral (Extravascular) Administration (Vz/F) of Acalabrutinib
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)
Metabolite-to-parent Molar Ratio for AUC0-t (MR_AUC0-t) of Acalabrutinib and ACP-5862
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)
Metabolite-to-parent Molar Ratio for AUC0-inf (MR_AUC0-inf) of Acalabrutinib and ACP-5862
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)
Metabolite-to-parent Molar Ratio for Cmax (MR_Cmax) of Acalabrutinib and ACP-5862
Time frame: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)
Incidence of Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: Day 1 through 30 days after the last dose of study drug (approximately 3. 5 months)
Incidences of Abnormal Vital Signs and Physical Examinations Reported as TEAEs
Time frame: Day 1 through 30 days after the last dose of study drug (approximately 3. 5 months)
Incidences of Abnormal Electrocardiograms (ECGs) Reported as TEAEs
Time frame: Day 1 through 30 days after the last dose of study drug (approximately 3. 5 months)
Incidences of Abnormal Clinical Laboratory Parameters Reported as TEAEs
Time frame: Day 1 through 30 days after the last dose of study drug (approximately 3. 5 months)