Healthy
Conditions
Brief summary
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.
Interventions
DRUGDigoxin
Administered Orally.
DRUGPirtobrutinib
Administered Orally.
Sponsors
Loxo Oncology, Inc.
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Must have Body mass index (BMI) within the range of 18.0 to 32.0 kilograms per square meter (kg/m²), inclusive * Male and female participants in good health, determined by no clinically significant findings from medical history, 12-lead Electrocardiogram (ECG), vital sign measurements, or clinical laboratory evaluations as assessed by the investigator * Female participants of non-childbearing potential and male participants who follow standard contraceptive methods * Must have comply with all study procedures, including the 20-night stay at the Clinical Research Unit (CRU) and follow-up phone call
Exclusion criteria
* History or presence of any diseases or conditions of clinical significance by the Investigator (or designee) and/or Sponsor * Positive serologic test for hepatitis B surface antigen (HBsAg), hepatitis B virus immunoglobulin M (HBV IgM) core antibody, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody at Screening * Positive polymerase chain reaction (PCR) test for COVID-19 at Screening or Check-in (Day -1) * Known ongoing alcohol and/or drug abuse within 2 years prior to Screening * History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee) * Have previously completed or withdrawn from any other study investigating Pirtobrutinib (LOXO-305) and have previously received the investigational product
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib in Plasma | 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: CL/F of Pirtobrutinib in plasma was reported. |
| Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC[0-t]) of Digoxin in Plasma | 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: AUC\[0-t\] of Digoxin was reported. |
| PK: Area Under the Concentration During a Dosing Interval (AUC [Tau]) of Digoxin in Plasma | 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: AUC \[tau\] of Digoxin was reported. |
| PK: Apparent Systemic Clearance (CL/F) of Digoxin in Plasma | 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: CL/F of Digoxin in plasma was reported. |
| PK: Maximum Observed Plasma Concentration (Cmax) of Digoxin in Plasma | 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: Cmax of Digoxin was reported. |
| PK: Time to Maximum Observed Plasma Concentration (Tmax) of Digoxin in Plasma | 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: Tmax of Digoxin was reported. |
| PK: Mean Residence Time (MRT) of Digoxin in Plasma | 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: MRT of Digoxin was reported. |
| PK: Cumulative Amount of Drug Excreted Unchanged in Urine (Ae) of Digoxin | Day 7 and Day 16: Predose, 6, 12, 24 hours post dose | 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. |
| PK: Fraction of Digoxin Excreted Unchanged in Urine (Fe) Expressed as Percentage of Dose Excreted | Day 7 and Day 16: Predose, 6, 12, 24 hours post dose | 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. |
| PK: Renal Clearance (CLr) of Digoxin in Plasma | 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: CLr of Digoxin in plasma was reported. |
| PK: Area Under the Concentration From Hour 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib in Plasma | 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: AUC\[0-t\] of Pirtobrutinib was reported. |
| PK: Area Under the Concentration During a Dosing Interval (AUCtau) of Pirtobrutinib in Plasma | 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: AUCtau of Pirtobrutinib was reported. |
| PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib in Plasma | 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: Cmax of Pirtobrutinib was reported. |
| PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib in Plasma | 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: Tmax of Pirtobrutinib was reported. |
| PK: Mean Residence Time (MRT) of Pirtobrutinib in Plasma | 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: MRT of Pirtobrutinib was reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Digoxin + Pirtobrutinib Participants received oral dose of
* 0.25 mg digoxin twice daily (BID) on Day 1
* 0.25 mg digoxin once daily (QD) from Day 2 to Day 7
* 200 mg Pirtobrutinib in combination with 0.25 mg digoxin QD starting from Day 8 to Day 16 | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Digoxin + Pirtobrutinib |
|---|---|
| Age, Continuous | 41.8 years STANDARD_DEVIATION 8.25 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 16 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 5 / 16 | 1 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
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
Population: All enrolled population who had received at least one dose of digoxin had at least one quantifiable PK concentration and for whom at least one PK parameter was computed. Number analyzed refer to participants evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Digoxin + Pirtobrutinib | Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC[0-t]) of Digoxin in Plasma | Day 7 | 14.6 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 21.1 |
| Digoxin + Pirtobrutinib | Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC[0-t]) of Digoxin in Plasma | Day 8 | 17.1 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 19.6 |
| Digoxin + Pirtobrutinib | Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration (AUC[0-t]) of Digoxin in Plasma | Day 16 | 48.9 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 22 |
Primary
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
Population: All enrolled population who had received at least one dose of digoxin had at least one quantifiable PK concentration and for whom at least one PK parameter was computed. Number analyzed refer to participants evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Digoxin + Pirtobrutinib | PK: Apparent Systemic Clearance (CL/F) of Digoxin in Plasma | Day 7 | 17.0 liter per hour(L/h) | Geometric Coefficient of Variation 21.1 |
| Digoxin + Pirtobrutinib | PK: Apparent Systemic Clearance (CL/F) of Digoxin in Plasma | Day 8 | 14.5 liter per hour(L/h) | Geometric Coefficient of Variation 19.6 |
| Digoxin + Pirtobrutinib | PK: Apparent Systemic Clearance (CL/F) of Digoxin in Plasma | Day 16 | 12.2 liter per hour(L/h) | Geometric Coefficient of Variation 23.4 |
Primary
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
Population: All enrolled population who had received at least one dose of Pirtobrutinib had at least one quantifiable PK concentration and for whom at least one PK parameter was computed. Number analyzed refer to participants evaluable at specified time points.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Digoxin + Pirtobrutinib | PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib in Plasma | 1.89 L/h | Geometric Coefficient of Variation 21 |
Primary
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
Population: All enrolled population who had received at least one dose of digoxin had at least one quantifiable PK concentration and for whom at least one PK parameter was computed. Number analyzed refer to participants evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Digoxin + Pirtobrutinib | PK: Area Under the Concentration During a Dosing Interval (AUC [Tau]) of Digoxin in Plasma | Day 7 | 14.7 h*ng/mL | Geometric Coefficient of Variation 21.1 |
| Digoxin + Pirtobrutinib | PK: Area Under the Concentration During a Dosing Interval (AUC [Tau]) of Digoxin in Plasma | Day 8 | 17.2 h*ng/mL | Geometric Coefficient of Variation 19.6 |
| Digoxin + Pirtobrutinib | PK: Area Under the Concentration During a Dosing Interval (AUC [Tau]) of Digoxin in Plasma | Day 16 | 20.4 h*ng/mL | Geometric Coefficient of Variation 23.4 |
Primary
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
Population: All enrolled population who had received at least one dose of Pirtobrutinib had at least one quantifiable PK concentration and for whom at least one PK parameter was computed. Number analyzed refer to participants evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Digoxin + Pirtobrutinib | PK: Area Under the Concentration During a Dosing Interval (AUCtau) of Pirtobrutinib in Plasma | Day 8 | 48600 h*ng/mL | Geometric Coefficient of Variation 16.3 |
| Digoxin + Pirtobrutinib | PK: Area Under the Concentration During a Dosing Interval (AUCtau) of Pirtobrutinib in Plasma | Day 16 | 106000 h*ng/mL | Geometric Coefficient of Variation 21 |
Primary
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
Population: All enrolled population who had received at least one dose of Pirtobrutinib had at least one quantifiable PK concentration and for whom at least one PK parameter was computed. Number analyzed refer to participants evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Digoxin + Pirtobrutinib | PK: Area Under the Concentration From Hour 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib in Plasma | Day 8 | 48400 h*ng/mL | Geometric Coefficient of Variation 16.3 |
| Digoxin + Pirtobrutinib | PK: Area Under the Concentration From Hour 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib in Plasma | Day 16 | 189000 h*ng/mL | Geometric Coefficient of Variation 25.8 |
Primary
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
Population: All enrolled population who had received at least one dose of digoxin had at least one quantifiable PK concentration and for whom at least one PK parameter was computed. Number analyzed refer to participants evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Digoxin + Pirtobrutinib | PK: Cumulative Amount of Drug Excreted Unchanged in Urine (Ae) of Digoxin | Day 7 | 0.123 mg | Geometric Coefficient of Variation 23.3 |
| Digoxin + Pirtobrutinib | PK: Cumulative Amount of Drug Excreted Unchanged in Urine (Ae) of Digoxin | Day 16 | 0.148 mg | Geometric Coefficient of Variation 18.2 |
Primary
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
Population: All enrolled population who had received at least one dose of digoxin had at least one quantifiable PK concentration and for whom at least one PK parameter was computed. Number analyzed refer to participants evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Digoxin + Pirtobrutinib | PK: Fraction of Digoxin Excreted Unchanged in Urine (Fe) Expressed as Percentage of Dose Excreted | Day 7 | 49.2 percentage of dose excreted in urine | Geometric Coefficient of Variation 23.3 |
| Digoxin + Pirtobrutinib | PK: Fraction of Digoxin Excreted Unchanged in Urine (Fe) Expressed as Percentage of Dose Excreted | Day 16 | 59.4 percentage of dose excreted in urine | Geometric Coefficient of Variation 18.2 |
Primary
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
Population: All enrolled population who had received at least one dose of digoxin had at least one quantifiable PK concentration and for whom at least one PK parameter was computed. Number analyzed refer to participants evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Digoxin + Pirtobrutinib | PK: Maximum Observed Plasma Concentration (Cmax) of Digoxin in Plasma | Day 7 | 1.57 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 26.1 |
| Digoxin + Pirtobrutinib | PK: Maximum Observed Plasma Concentration (Cmax) of Digoxin in Plasma | Day 8 | 2.38 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 27.7 |
| Digoxin + Pirtobrutinib | PK: Maximum Observed Plasma Concentration (Cmax) of Digoxin in Plasma | Day 16 | 2.45 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 42 |
Primary
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
Population: All enrolled population who had received at least one dose of Pirtobrutinib had at least one quantifiable PK concentration and for whom at least one PK parameter was computed. Number analyzed refer to participants evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Digoxin + Pirtobrutinib | PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib in Plasma | Day 16 | 7530 ng/mL | Geometric Coefficient of Variation 17.9 |
| Digoxin + Pirtobrutinib | PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib in Plasma | Day 8 | 4330 ng/mL | Geometric Coefficient of Variation 17.1 |
Primary
PK: Mean Residence Time (MRT) of Digoxin in Plasma
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
Population: All enrolled population who had received at least one dose of digoxin had at least one quantifiable PK concentration and for whom at least one PK parameter was computed. Number analyzed refer to participants evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Digoxin + Pirtobrutinib | PK: Mean Residence Time (MRT) of Digoxin in Plasma | Day 7 | 52.2 hours | Geometric Coefficient of Variation 49.1 |
| Digoxin + Pirtobrutinib | PK: Mean Residence Time (MRT) of Digoxin in Plasma | Day 8 | 65.2 hours | Geometric Coefficient of Variation 47.2 |
| Digoxin + Pirtobrutinib | PK: Mean Residence Time (MRT) of Digoxin in Plasma | Day 16 | 60.4 hours | Geometric Coefficient of Variation 52.5 |
Primary
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
Population: All enrolled population who had received at least one dose of Pirtobrutinib had at least one quantifiable PK concentration and for whom at least one PK parameter was computed. Number analyzed refer to participants evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Digoxin + Pirtobrutinib | PK: Mean Residence Time (MRT) of Pirtobrutinib in Plasma | Day 8 | 22.6 hours | Geometric Coefficient of Variation 18.7 |
| Digoxin + Pirtobrutinib | PK: Mean Residence Time (MRT) of Pirtobrutinib in Plasma | Day 16 | 30.5 hours | Geometric Coefficient of Variation 17.5 |
Primary
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
Population: All enrolled population who had received at least one dose of digoxin had at least one quantifiable PK concentration and for whom at least one PK parameter was computed. Number analyzed refer to participants evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Digoxin + Pirtobrutinib | PK: Renal Clearance (CLr) of Digoxin in Plasma | Day 7 | 8.35 L/h | Geometric Coefficient of Variation 15 |
| Digoxin + Pirtobrutinib | PK: Renal Clearance (CLr) of Digoxin in Plasma | Day 16 | 7.28 L/h | Geometric Coefficient of Variation 17 |
Primary
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
Population: All enrolled population who had received at least one dose of digoxin had at least one quantifiable PK concentration and for whom at least one PK parameter was computed. Number analyzed refer to participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Digoxin + Pirtobrutinib | PK: Time to Maximum Observed Plasma Concentration (Tmax) of Digoxin in Plasma | Day 7 | 1.27 hour |
| Digoxin + Pirtobrutinib | PK: Time to Maximum Observed Plasma Concentration (Tmax) of Digoxin in Plasma | Day 8 | 1.25 hour |
| Digoxin + Pirtobrutinib | PK: Time to Maximum Observed Plasma Concentration (Tmax) of Digoxin in Plasma | Day 16 | 1.00 hour |
Primary
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
Population: All enrolled population who had received at least one dose of Pirtobrutinib had at least one quantifiable PK concentration and for whom at least one PK parameter was computed. Number analyzed refer to participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Digoxin + Pirtobrutinib | PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib in Plasma | Day 8 | 2.50 hours |
| Digoxin + Pirtobrutinib | PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib in Plasma | Day 16 | 2.50 hours |