The main purpose of this study is to evaluate the effect of Pirtobrutinib (LOXO-305) on multiple oral doses of digoxin (P-gp substrate) when administered as single and multiple doses by collecting the blood samples and conducting the blood tests to measure how much digoxin is in the bloodstream and how the body handles and eliminates it in healthy participants. The study will also evaluate the safety and tolerability of Pirtobrutinib. Participants will stay in this study for up to 58 days, including screening.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
16
Administered Orally.
Administered Orally.
Covance Clinical Research Unit
Madison, Wisconsin, United States
Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC[0-t]) of Digoxin in Plasma
PK: AUC\[0-t\] of Digoxin was reported.
Time frame: Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: Area Under the Concentration During a Dosing Interval (AUC [Tau]) of Digoxin in Plasma
PK: AUC \[tau\] of Digoxin was reported.
Time frame: Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: Apparent Systemic Clearance (CL/F) of Digoxin in Plasma
PK: CL/F of Digoxin in plasma was reported.
Time frame: Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: Maximum Observed Plasma Concentration (Cmax) of Digoxin in Plasma
PK: Cmax of Digoxin was reported.
Time frame: Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: Time to Maximum Observed Plasma Concentration (Tmax) of Digoxin in Plasma
PK: Tmax of Digoxin was reported.
Time frame: Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: Mean Residence Time (MRT) of Digoxin in Plasma
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PK: MRT of Digoxin was reported.
Time frame: Day 7 and Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: Cumulative Amount of Drug Excreted Unchanged in Urine (Ae) of Digoxin
PK: Ae of Digoxin in urine was reported. The urine sampling time points from pre-dose through 24 hours post-dose were used to assess this outcome.
Time frame: Day 7 and Day 16: Predose, 6, 12, 24 hours post dose
PK: Fraction of Digoxin Excreted Unchanged in Urine (Fe) Expressed as Percentage of Dose Excreted
PK: Fe of Digoxin was reported. The urine sampling time points from pre-dose through 24 hours post-dose were used to assess this outcome.
Time frame: Day 7 and Day 16: Predose, 6, 12, 24 hours post dose
PK: Renal Clearance (CLr) of Digoxin in Plasma
PK: CLr of Digoxin in plasma was reported.
Time frame: Day 7: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: Area Under the Concentration From Hour 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib in Plasma
PK: AUC\[0-t\] of Pirtobrutinib was reported.
Time frame: Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: Area Under the Concentration During a Dosing Interval (AUCtau) of Pirtobrutinib in Plasma
PK: AUCtau of Pirtobrutinib was reported.
Time frame: Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib in Plasma
PK: CL/F of Pirtobrutinib in plasma was reported.
Time frame: Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib in Plasma
PK: Cmax of Pirtobrutinib was reported.
Time frame: Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib in Plasma
PK: Tmax of Pirtobrutinib was reported.
Time frame: Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose
PK: Mean Residence Time (MRT) of Pirtobrutinib in Plasma
PK: MRT of Pirtobrutinib was reported.
Time frame: Day 8: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose; Day 16: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose