Healthy
Conditions
Brief summary
The main purpose of this study is to evaluate the effect of LOXO-305 on single oral dose of caffeine cytochrome P450 1A2 (CYP1A2) substrate, S-warfarin (CYP2C9 substrate), and omeprazole (CYP2C19 substrate) when administered as multiple doses by collecting the blood samples and conducting the blood tests to measure how much LOXO-305 is in the bloodstream and how the body handles and eliminates LOXO-305 in adult healthy participants. The study will also evaluate the safety and tolerability of LOXO-305. The study will be conducted in two periods. Participants will stay in this study for up to 67 days, including screening.
Interventions
DRUGCaffeine Tablet
Administered orally.
Administered orally.
DRUGWarfarin tablet
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/m\^2), 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 23-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. * 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Caffeine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | Area under the concentration time curve (AUC) from hour 0 to 24 hours post-dose (AUC0-24) of caffeine was reported. |
| Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Paraxanthine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | AUC0-24 of Paraxanthine was reported. |
| Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Omeprazole | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | AUC0-24 of Omeprazole was reported. |
| Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Warfarin | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | AUC(0-24) of Warfarin was reported. |
| Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Pirtobrutinib | Period 2, Day 15 (0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours Post dose) | AUC0-24 of Pirtobrutinib was reported. |
| Area Under the Concentration-time Curve (AUC), From Hour 0 to the Last Measurable Concentration (AUC0-t): Caffeine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | AUC from hour 0 to the last measurable concentration (AUC0-t) of caffeine was reported. |
| Area Under the Concentration-time Curve (AUC), From Hour 0 to the Last Measurable Concentration (AUC0-t): Paraxanthine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | AUC0-t of Paraxanthine was reported. |
| Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Omeprazole | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose) | AUC0-t of Omeprazole was reported. |
| Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Warfarin | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose) | AUC0-t of Warfarin was reported. |
| Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Pirtobrutinib | Period 2, Day 15 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours postdose) | AUC0-t of Pirtobrutinib was reported. |
| Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Caffeine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | AUC from hour 0 extrapolated to infinity (AUC0-inf) of Caffeine was reported. |
| Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Paraxanthine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | AUC0-inf of Paraxanthine was reported. |
| Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Omeprazole | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose) | AUC0-inf of omeprazole was reported. |
| Percentage Extrapolation for AUC0-inf (%AUCextrap): Paraxanthine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | AUC0-inf (%AUCextrap) of Paraxanthine was reported. |
| Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Warfarin | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose) | AUC0-inf of Warfarin was reported. |
| Percentage Extrapolation for AUC0-inf (%AUCextrap): Caffeine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | AUC0-inf (%AUCextrap) of caffeine was reported. |
| Percentage Extrapolation for AUC0-inf (%AUCextrap): Omeprazole | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose) | %AUCextrap of omeprazole was reported. |
| Percentage Extrapolation for AUC0-inf (%AUCextrap): Warfarin | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose) | %AUCextrap of Warfarin was reported. |
| Apparent Systemic Clearance (CL/F): Caffeine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | CL/F for caffeine was reported. |
| Apparent Systemic Clearance (CL/F): Omeprazole | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose) | CL/F of omeprazole was reported. |
| Apparent Systemic Clearance (CL/F): Warfarin | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose) | CL/F of warfarin was reported. |
| Apparent Systemic Clearance (CL/F): Pirtobrutinib | Period 2, Day 15 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours postdose) | CL/F of Pirtobrutinib was reported. |
| Maximum Observed Plasma Concentration (Cmax): Caffeine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | Cmax of caffeine was reported. |
| Maximum Observed Plasma Concentration (Cmax): Paraxanthine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | Cmax of Paraxanthine was reported. |
| Maximum Observed Plasma Concentration (Cmax): Omeprazole | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose) | Cmax of omeprazole was reported. |
| Mean Residence Time (MRT): Paraxanthine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | MRT of Paraxanthine was reported. |
| Maximum Observed Plasma Concentration (Cmax): Warfarin | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose) | Cmax of warfarin was reported. |
| Maximum Observed Plasma Concentration (Cmax): Pirtobrutinib | Period 2, Day 15 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours postdose) | Cmax of Pirtobrutinib was reported. |
| Time to Maximum Observed Plasma Concentration (Tmax): Caffeine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | Tmax of caffeine was reported. |
| Time to Maximum Observed Plasma Concentration (Tmax): Paraxanthine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | Tmax of Paraxanthine was reported. |
| Time to Maximum Observed Plasma Concentration (Tmax): Omeprazole | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose) | Tmax of omeprazole was reported. |
| Time to Maximum Observed Plasma Concentration (Tmax): Warfarin | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose) | Tmax of warfarin was reported. |
| Time to Maximum Observed Plasma Concentration (Tmax): Pirtobrutinib | Period 2, Day 15 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours postdose) | Tmax of Pirtobrutinib was reported. |
| Apparent Terminal Elimination Rate Constant (λZ): Caffeine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | λZ of caffeine was reported. |
| Apparent Terminal Elimination Rate Constant (λZ): Paraxanthine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | λZ of Paraxanthine was reported. |
| Apparent Terminal Elimination Rate Constant (λZ): Omeprazole | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose) | λZ of omeprazole was reported. |
| Apparent Terminal Elimination Rate Constant (λZ): Warfarin | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose) | λZ of warfarin was reported. |
| Apparent Volume of Distribution at Terminal Phase (Vz/F): Caffeine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | Vz/F of caffeine was reported. |
| Apparent Volume of Distribution at Terminal Phase (Vz/F): Omeprazole | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose) | Vz/F of omeprazole was reported. |
| Apparent Volume of Distribution at Terminal Phase (Vz/F): Warfarin | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose) | Vz/F of Warfarin was reported. |
| Metabolite to Parent Drug AUC Ratio (MRAUC): AUC Ratio of Paraxanthine to Caffeine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | AUC Ratio of paraxanthine (Metabolite) to caffeine (Parent drug) was reported. |
| Mean Residence Time (MRT): Caffeine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | MRT of caffeine was reported. |
| Mean Residence Time (MRT): Omeprazole | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose) | MRT of omeprazole was reported. |
| Mean Residence Time (MRT): Warfarin | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose) | MRT of warfarin was reported. |
| Apparent Terminal Elimination Half-Life (t1/2): Caffeine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | t1/2 of caffeine was reported. |
| Apparent Terminal Elimination Half-Life (t1/2): Paraxanthine | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose) | t1/2 of Paraxanthine was reported. |
| Apparent Terminal Elimination Half-Life (t1/2): Omeprazole | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose) | t1/2 of omeprazole was reported. |
| Apparent Terminal Elimination Half-Life (t1/2): Warfarin | Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose) | t1/2 of warfarin was reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Participants * Period 1: Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.
* Period 2: Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet.
* There was a 5-day washout period between the probe drug cocktail on Day 1 (Period 1) and the first dose of Pirtobrutinib on Day 6 (Period 2). | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Overall Study Participants |
|---|---|
| Age, Continuous | 39.1 years STANDARD_DEVIATION 9.46 |
| 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 | 7 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 | 9 Participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 3 / 16 | 8 / 16 | 1 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 16 |
Outcome results
Primary
Apparent Systemic Clearance (CL/F): Caffeine
CL/F for caffeine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Apparent Systemic Clearance (CL/F): Caffeine | 4.70 Liter per hour (L/h) | Geometric Coefficient of Variation 39.7 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Apparent Systemic Clearance (CL/F): Caffeine | 5.00 Liter per hour (L/h) | Geometric Coefficient of Variation 37.5 |
Primary
Apparent Systemic Clearance (CL/F): Omeprazole
CL/F of omeprazole was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Apparent Systemic Clearance (CL/F): Omeprazole | 20.0 L/h | Geometric Coefficient of Variation 101 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Apparent Systemic Clearance (CL/F): Omeprazole | 12.8 L/h | Geometric Coefficient of Variation 61.6 |
Primary
Apparent Systemic Clearance (CL/F): Pirtobrutinib
CL/F of Pirtobrutinib was reported.
Time frame: Period 2, Day 15 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Apparent Systemic Clearance (CL/F): Pirtobrutinib | 1.68 L/h | Geometric Coefficient of Variation 24.4 |
Primary
Apparent Systemic Clearance (CL/F): Warfarin
CL/F of warfarin was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Apparent Systemic Clearance (CL/F): Warfarin | 0.497 L/h | Geometric Coefficient of Variation 21.1 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Apparent Systemic Clearance (CL/F): Warfarin | 0.447 L/h | Geometric Coefficient of Variation 21.9 |
Primary
Apparent Terminal Elimination Half-Life (t1/2): Caffeine
t1/2 of caffeine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Apparent Terminal Elimination Half-Life (t1/2): Caffeine | 5.96 hour (h) | Geometric Coefficient of Variation 37.8 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Apparent Terminal Elimination Half-Life (t1/2): Caffeine | 5.47 hour (h) | Geometric Coefficient of Variation 34.6 |
Primary
Apparent Terminal Elimination Half-Life (t1/2): Omeprazole
t1/2 of omeprazole was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Apparent Terminal Elimination Half-Life (t1/2): Omeprazole | 1.13 hour (h) | Geometric Coefficient of Variation 48.4 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Apparent Terminal Elimination Half-Life (t1/2): Omeprazole | 1.20 hour (h) | Geometric Coefficient of Variation 37.2 |
Primary
Apparent Terminal Elimination Half-Life (t1/2): Paraxanthine
t1/2 of Paraxanthine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed. Here 'overall number of participants analyzed' signifies participants with available data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Apparent Terminal Elimination Half-Life (t1/2): Paraxanthine | 7.17 hour (h) | Geometric Coefficient of Variation 24 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Apparent Terminal Elimination Half-Life (t1/2): Paraxanthine | 5.79 hour (h) | Geometric Coefficient of Variation 21.8 |
Primary
Apparent Terminal Elimination Half-Life (t1/2): Warfarin
t1/2 of warfarin was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Apparent Terminal Elimination Half-Life (t1/2): Warfarin | 43.2 hour (h) | Geometric Coefficient of Variation 17.1 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Apparent Terminal Elimination Half-Life (t1/2): Warfarin | 42.0 hour (h) | Geometric Coefficient of Variation 16.4 |
Primary
Apparent Terminal Elimination Rate Constant (λZ): Caffeine
λZ of caffeine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Apparent Terminal Elimination Rate Constant (λZ): Caffeine | 0.116 1/hour (1/h) | Geometric Coefficient of Variation 37.8 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Apparent Terminal Elimination Rate Constant (λZ): Caffeine | 0.127 1/hour (1/h) | Geometric Coefficient of Variation 34.6 |
Primary
Apparent Terminal Elimination Rate Constant (λZ): Omeprazole
λZ of omeprazole was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Apparent Terminal Elimination Rate Constant (λZ): Omeprazole | 0.611 1/hour (1/h) | Geometric Coefficient of Variation 48.4 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Apparent Terminal Elimination Rate Constant (λZ): Omeprazole | 0.578 1/hour (1/h) | Geometric Coefficient of Variation 37.2 |
Primary
Apparent Terminal Elimination Rate Constant (λZ): Paraxanthine
λZ of Paraxanthine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed. Here 'overall number of participants analyzed' signifies participants with available data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Apparent Terminal Elimination Rate Constant (λZ): Paraxanthine | 0.0966 1/hour (1/h) | Geometric Coefficient of Variation 24 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Apparent Terminal Elimination Rate Constant (λZ): Paraxanthine | 0.120 1/hour (1/h) | Geometric Coefficient of Variation 21.8 |
Primary
Apparent Terminal Elimination Rate Constant (λZ): Warfarin
λZ of warfarin was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Apparent Terminal Elimination Rate Constant (λZ): Warfarin | 0.0160 1/hour (1/h) | Geometric Coefficient of Variation 17.1 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Apparent Terminal Elimination Rate Constant (λZ): Warfarin | 0.0165 1/hour (1/h) | Geometric Coefficient of Variation 16.4 |
Primary
Apparent Volume of Distribution at Terminal Phase (Vz/F): Caffeine
Vz/F of caffeine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Apparent Volume of Distribution at Terminal Phase (Vz/F): Caffeine | 40.4 Litre (L) | Geometric Coefficient of Variation 16.8 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Apparent Volume of Distribution at Terminal Phase (Vz/F): Caffeine | 39.4 Litre (L) | Geometric Coefficient of Variation 18.1 |
Primary
Apparent Volume of Distribution at Terminal Phase (Vz/F): Omeprazole
Vz/F of omeprazole was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Apparent Volume of Distribution at Terminal Phase (Vz/F): Omeprazole | 32.8 Litre (L) | Geometric Coefficient of Variation 45.7 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Apparent Volume of Distribution at Terminal Phase (Vz/F): Omeprazole | 22.2 Litre (L) | Geometric Coefficient of Variation 33.6 |
Primary
Apparent Volume of Distribution at Terminal Phase (Vz/F): Warfarin
Vz/F of Warfarin was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Apparent Volume of Distribution at Terminal Phase (Vz/F): Warfarin | 31.0 Litre (L) | Geometric Coefficient of Variation 18.4 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Apparent Volume of Distribution at Terminal Phase (Vz/F): Warfarin | 27.1 Litre (L) | Geometric Coefficient of Variation 21 |
Primary
Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Caffeine
AUC from hour 0 extrapolated to infinity (AUC0-inf) of Caffeine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Caffeine | 42600 h*ng/mL | Geometric Coefficient of Variation 39.7 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Caffeine | 40000 h*ng/mL | Geometric Coefficient of Variation 37.5 |
Primary
Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Omeprazole
AUC0-inf of omeprazole was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Omeprazole | 2000 h*ng/mL | Geometric Coefficient of Variation 101 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Omeprazole | 3120 h*ng/mL | Geometric Coefficient of Variation 61.6 |
Primary
Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Paraxanthine
AUC0-inf of Paraxanthine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed. Here 'overall number of participants analyzed' signifies participants with available data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Paraxanthine | 23100 h*ng/mL | Geometric Coefficient of Variation 10.1 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Paraxanthine | 20300 h*ng/mL | Geometric Coefficient of Variation 17.4 |
Primary
Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Warfarin
AUC0-inf of Warfarin was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Warfarin | 20100 h*ng/mL | Geometric Coefficient of Variation 21.1 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Warfarin | 22400 h*ng/mL | Geometric Coefficient of Variation 21.9 |
Primary
Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Caffeine
Area under the concentration time curve (AUC) from hour 0 to 24 hours post-dose (AUC0-24) of caffeine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Caffeine | 39100 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 31.8 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Caffeine | 37400 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 31.8 |
Primary
Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Omeprazole
AUC0-24 of Omeprazole was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Omeprazole | 2000 h*ng/mL | Geometric Coefficient of Variation 100.9 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Omeprazole | 3120 h*ng/mL | Geometric Coefficient of Variation 61.6 |
Primary
Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Paraxanthine
AUC0-24 of Paraxanthine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed. Here 'overall number of participants analyzed' signifies participants with available data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Paraxanthine | 20600 h*ng/mL | Geometric Coefficient of Variation 12.1 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Paraxanthine | 18600 h*ng/mL | Geometric Coefficient of Variation 17.7 |
Primary
Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Pirtobrutinib
AUC0-24 of Pirtobrutinib was reported.
Time frame: Period 2, Day 15 (0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours Post dose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Pirtobrutinib | 119000 h*ng/mL | Geometric Coefficient of Variation 24.4 |
Primary
Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Warfarin
AUC(0-24) of Warfarin was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Warfarin | 7320 h*ng/mL | Geometric Coefficient of Variation 19.7 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Warfarin | 7880 h*ng/mL | Geometric Coefficient of Variation 18.3 |
Primary
Area Under the Concentration-time Curve (AUC), From Hour 0 to the Last Measurable Concentration (AUC0-t): Caffeine
AUC from hour 0 to the last measurable concentration (AUC0-t) of caffeine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Area Under the Concentration-time Curve (AUC), From Hour 0 to the Last Measurable Concentration (AUC0-t): Caffeine | 39100 h*ng/mL | Geometric Coefficient of Variation 31.8 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Area Under the Concentration-time Curve (AUC), From Hour 0 to the Last Measurable Concentration (AUC0-t): Caffeine | 37400 h*ng/mL | Geometric Coefficient of Variation 31.7 |
Primary
Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Omeprazole
AUC0-t of Omeprazole was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Omeprazole | 1990 h*ng/mL | Geometric Coefficient of Variation 101 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Omeprazole | 3110 h*ng/mL | Geometric Coefficient of Variation 61.7 |
Primary
Area Under the Concentration-time Curve (AUC), From Hour 0 to the Last Measurable Concentration (AUC0-t): Paraxanthine
AUC0-t of Paraxanthine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Area Under the Concentration-time Curve (AUC), From Hour 0 to the Last Measurable Concentration (AUC0-t): Paraxanthine | 20600 h*ng/mL | Geometric Coefficient of Variation 12.1 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Area Under the Concentration-time Curve (AUC), From Hour 0 to the Last Measurable Concentration (AUC0-t): Paraxanthine | 19400 h*ng/mL | Geometric Coefficient of Variation 14 |
Primary
Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Pirtobrutinib
AUC0-t of Pirtobrutinib was reported.
Time frame: Period 2, Day 15 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Pirtobrutinib | 119000 h*ng/mL | Geometric Coefficient of Variation 24.4 |
Primary
Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Warfarin
AUC0-t of Warfarin was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Warfarin | 17300 h*ng/mL | Geometric Coefficient of Variation 19.1 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Warfarin | 19200 h*ng/mL | Geometric Coefficient of Variation 20 |
Primary
Maximum Observed Plasma Concentration (Cmax): Caffeine
Cmax of caffeine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Maximum Observed Plasma Concentration (Cmax): Caffeine | 5060 ng/mL | Geometric Coefficient of Variation 17.6 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Maximum Observed Plasma Concentration (Cmax): Caffeine | 4990 ng/mL | Geometric Coefficient of Variation 14.5 |
Primary
Maximum Observed Plasma Concentration (Cmax): Omeprazole
Cmax of omeprazole was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Maximum Observed Plasma Concentration (Cmax): Omeprazole | 901 ng/mL | Geometric Coefficient of Variation 58 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Maximum Observed Plasma Concentration (Cmax): Omeprazole | 1350 ng/mL | Geometric Coefficient of Variation 42.3 |
Primary
Maximum Observed Plasma Concentration (Cmax): Paraxanthine
Cmax of Paraxanthine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Maximum Observed Plasma Concentration (Cmax): Paraxanthine | 1200 ng/mL | Geometric Coefficient of Variation 14.3 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Maximum Observed Plasma Concentration (Cmax): Paraxanthine | 1150 ng/mL | Geometric Coefficient of Variation 14.6 |
Primary
Maximum Observed Plasma Concentration (Cmax): Pirtobrutinib
Cmax of Pirtobrutinib was reported.
Time frame: Period 2, Day 15 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Maximum Observed Plasma Concentration (Cmax): Pirtobrutinib | 9430 ng/mL | Geometric Coefficient of Variation 24.6 |
Primary
Maximum Observed Plasma Concentration (Cmax): Warfarin
Cmax of warfarin was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Maximum Observed Plasma Concentration (Cmax): Warfarin | 585 ng/mL | Geometric Coefficient of Variation 26.1 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Maximum Observed Plasma Concentration (Cmax): Warfarin | 595 ng/mL | Geometric Coefficient of Variation 25.2 |
Primary
Mean Residence Time (MRT): Caffeine
MRT of caffeine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Mean Residence Time (MRT): Caffeine | 8.58 hour (h) | Geometric Coefficient of Variation 35.8 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Mean Residence Time (MRT): Caffeine | 8.03 hour (h) | Geometric Coefficient of Variation 30.9 |
Primary
Mean Residence Time (MRT): Omeprazole
MRT of omeprazole was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Mean Residence Time (MRT): Omeprazole | 3.22 hour (h) | Geometric Coefficient of Variation 32.4 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Mean Residence Time (MRT): Omeprazole | 3.58 hour (h) | Geometric Coefficient of Variation 20.1 |
Primary
Mean Residence Time (MRT): Paraxanthine
MRT of Paraxanthine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Mean Residence Time (MRT): Paraxanthine | 12.8 hour (h) | Geometric Coefficient of Variation 18.3 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Mean Residence Time (MRT): Paraxanthine | 10.9 hour (h) | Geometric Coefficient of Variation 14.8 |
Primary
Mean Residence Time (MRT): Warfarin
MRT of warfarin was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Mean Residence Time (MRT): Warfarin | 56.8 hour (h) | Geometric Coefficient of Variation 18.9 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Mean Residence Time (MRT): Warfarin | 57.9 hour (h) | Geometric Coefficient of Variation 18.7 |
Primary
Metabolite to Parent Drug AUC Ratio (MRAUC): AUC Ratio of Paraxanthine to Caffeine
AUC Ratio of paraxanthine (Metabolite) to caffeine (Parent drug) was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Metabolite to Parent Drug AUC Ratio (MRAUC): AUC Ratio of Paraxanthine to Caffeine | 0.528 Ratio | Geometric Coefficient of Variation 29.1 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Metabolite to Parent Drug AUC Ratio (MRAUC): AUC Ratio of Paraxanthine to Caffeine | 0.518 Ratio | Geometric Coefficient of Variation 27.8 |
Primary
Percentage Extrapolation for AUC0-inf (%AUCextrap): Caffeine
AUC0-inf (%AUCextrap) of caffeine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Percentage Extrapolation for AUC0-inf (%AUCextrap): Caffeine | 5.20 percentage of AUCextrap | Geometric Coefficient of Variation 130.6 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Percentage Extrapolation for AUC0-inf (%AUCextrap): Caffeine | 4.17 percentage of AUCextrap | Geometric Coefficient of Variation 149.3 |
Primary
Percentage Extrapolation for AUC0-inf (%AUCextrap): Omeprazole
%AUCextrap of omeprazole was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Percentage Extrapolation for AUC0-inf (%AUCextrap): Omeprazole | 0.421 percentage of AUCextrap | Geometric Coefficient of Variation 84.3 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Percentage Extrapolation for AUC0-inf (%AUCextrap): Omeprazole | 0.302 percentage of AUCextrap | Geometric Coefficient of Variation 97.8 |
Primary
Percentage Extrapolation for AUC0-inf (%AUCextrap): Paraxanthine
AUC0-inf (%AUCextrap) of Paraxanthine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed. Here 'overall number of participants analyzed' signifies participants with available data for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Percentage Extrapolation for AUC0-inf (%AUCextrap): Paraxanthine | 12.0 percentage of AUCextrap | Geometric Coefficient of Variation 58.3 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Percentage Extrapolation for AUC0-inf (%AUCextrap): Paraxanthine | 7.45 percentage of AUCextrap | Geometric Coefficient of Variation 63.6 |
Primary
Percentage Extrapolation for AUC0-inf (%AUCextrap): Warfarin
%AUCextrap of Warfarin was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Probe Drug Cocktail | Percentage Extrapolation for AUC0-inf (%AUCextrap): Warfarin | 13.1 percentage of AUCextrap | Geometric Coefficient of Variation 33.5 |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Percentage Extrapolation for AUC0-inf (%AUCextrap): Warfarin | 13.4 percentage of AUCextrap | Geometric Coefficient of Variation 32.7 |
Primary
Time to Maximum Observed Plasma Concentration (Tmax): Caffeine
Tmax of caffeine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Period 1: Probe Drug Cocktail | Time to Maximum Observed Plasma Concentration (Tmax): Caffeine | 0.500 hour (h) |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Time to Maximum Observed Plasma Concentration (Tmax): Caffeine | 0.750 hour (h) |
Primary
Time to Maximum Observed Plasma Concentration (Tmax): Omeprazole
Tmax of omeprazole was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Population: All participants who received a dose of study drug had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Period 1: Probe Drug Cocktail | Time to Maximum Observed Plasma Concentration (Tmax): Omeprazole | 2.00 hour (h) |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Time to Maximum Observed Plasma Concentration (Tmax): Omeprazole | 2.50 hour (h) |
Primary
Time to Maximum Observed Plasma Concentration (Tmax): Paraxanthine
Tmax of Paraxanthine was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Period 1: Probe Drug Cocktail | Time to Maximum Observed Plasma Concentration (Tmax): Paraxanthine | 10.0 hour (h) |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Time to Maximum Observed Plasma Concentration (Tmax): Paraxanthine | 8.01 hour (h) |
Primary
Time to Maximum Observed Plasma Concentration (Tmax): Pirtobrutinib
Tmax of Pirtobrutinib was reported.
Time frame: Period 2, Day 15 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Period 1: Probe Drug Cocktail | Time to Maximum Observed Plasma Concentration (Tmax): Pirtobrutinib | 2.50 hour (h) |
Primary
Time to Maximum Observed Plasma Concentration (Tmax): Warfarin
Tmax of warfarin was reported.
Time frame: Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Population: All participants who received a dose of study drug, had at least 1 quantifiable plasma concentration, and for whom at least 1 PK parameter could be computed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Period 1: Probe Drug Cocktail | Time to Maximum Observed Plasma Concentration (Tmax): Warfarin | 1.50 hour (h) |
| Period 2: Pirtobrutinib + Probe Drug Cocktail | Time to Maximum Observed Plasma Concentration (Tmax): Warfarin | 1.50 hour (h) |